Mult. SNPs(135) Track Settings
 
Simple Nucleotide Polymorphisms (dbSNP 135) That Map to Multiple Genomic Loci   (All Variation tracks)

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Include Chimp state and observed human alleles in name:  
(If enabled, chimp allele is displayed first, then '>', then human alleles).

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+  Filtering Options

+  Coloring Options
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Data last updated: 2013-08-19

Description

This track contains information about a subset of the single nucleotide polymorphisms and small insertions and deletions (indels) — collectively Simple Nucleotide Polymorphisms — from dbSNP build 135, available from ftp.ncbi.nih.gov/snp. Only SNPs that have been mapped to multiple locations in the reference genome assembly are included in this subset. When a SNP's flanking sequences map to multiple locations in the reference genome, it calls into question whether there is true variation at those sites, or whether the sequences at those sites are merely highly similar but not identical.

The default maximum weight for this track is 3, unlike the other dbSNP build 135 tracks which have a maximum weight of 1. That enables these multiply-mapped SNPs to appear in the display, while by default they will not appear in the All SNPs(135) track because of its maximum weight filter.

The remainder of this page is identical on the following tracks:
  • Common SNPs(135) - SNPs with >= 1% minor allele frequency (MAF), mapping only once to reference assembly.
  • Flagged SNPs(135) - SNPs < 1% minor allele frequency (MAF) (or unknown), mapping only once to reference assembly, flagged in dbSnp as "clinically associated" -- not necessarily a risk allele!
  • Mult. SNPs(135) - SNPs mapping in more than one place on reference assembly.
  • All SNPs(135) - all SNPs from dbSNP mapping to reference assembly.

Interpreting and Configuring the Graphical Display

Variants are shown as single tick marks at most zoom levels. When viewing the track at or near base-level resolution, the displayed width of the SNP corresponds to the width of the variant in the reference sequence. Insertions are indicated by a single tick mark displayed between two nucleotides, single nucleotide polymorphisms are displayed as the width of a single base, and multiple nucleotide variants are represented by a block that spans two or more bases.

On the track controls page, SNPs can be colored and/or filtered from the display according to several attributes:

  • Class: Describes the observed alleles
    • Single - single nucleotide variation: all observed alleles are single nucleotides (can have 2, 3 or 4 alleles)
    • In-del - insertion/deletion
    • Heterozygous - heterozygous (undetermined) variation: allele contains string '(heterozygous)'
    • Microsatellite - the observed allele from dbSNP is a variation in counts of short tandem repeats
    • Named - the observed allele from dbSNP is given as a text name instead of raw sequence, e.g., (Alu)/-
    • No Variation - the submission reports an invariant region in the surveyed sequence
    • Mixed - the cluster contains submissions from multiple classes
    • Multiple Nucleotide Polymorphism (MNP) - the alleles are all of the same length, and length > 1
    • Insertion - the polymorphism is an insertion relative to the reference assembly
    • Deletion - the polymorphism is a deletion relative to the reference assembly
    • Unknown - no classification provided by data contributor
  • Validation: Method used to validate the variant (each variant may be validated by more than one method)
    • By Frequency - at least one submitted SNP in cluster has frequency data submitted
    • By Cluster - cluster has at least 2 submissions, with at least one submission assayed with a non-computational method
    • By Submitter - at least one submitter SNP in cluster was validated by independent assay
    • By 2 Hit/2 Allele - all alleles have been observed in at least 2 chromosomes
    • By HapMap - submitted by HapMap project (human only)
    • By 1000Genomes - submitted by 1000Genomes project (human only)
    • Unknown - no validation has been reported for this variant
  • Function: dbSNP's predicted functional effect of variant on RefSeq transcripts, both curated (NM_* and NR_*) as in the RefSeq Genes track and predicted (XM_* and XR_*), not shown in UCSC Genome Browser. A variant may have more than one functional role if it overlaps multiple transcripts. For filtering and coloring, function terms are grouped into more general categories:
    • Locus Region - variation is 3' to and within 500 bases of a transcript, or is 5' to and within 2000 bases of a transcript (dbSNP terms: near-gene-3, near-gene-5; Sequence Ontology terms: downstream_gene_variant, upstream_gene_variant)
    • Coding - Synonymous - no change in peptide for allele with respect to the reference assembly (dbSNP term: coding-synon; Sequence Ontology term: synonymous_variant)
    • Coding - Non-Synonymous - change in peptide for allele with respect to the reference assembly (dbSNP terms: nonsense, missense, stop-loss, frameshift, cds-indel; Sequence Ontology terms: stop_gained, missense_variant, stop_lost, frameshift_variant, inframe_indel)
    • Untranslated - variation is in a transcript, but not in a coding region interval (dbSNP terms: untranslated-3, untranslated-5; Sequence Ontology terms: 3_prime_UTR_variant, 5_prime_UTR_variant)
    • Intron - variation is in an intron, but not in the first two or last two bases of the intron (dbSNP term: intron; Sequence Ontology term: intron_variant)
    • Splice Site - variation is in the first two or last two bases of an intron (dbSNP terms: splice-3, splice-5; Sequence Ontology terms: splice_acceptor_variant, splice_donor_variant)
      Note: splice-3/splice_acceptor_variant was not actually assigned to any variants in dbSNP build 135; splice-5/splice_donor_variant was assigned to only 11 variants.
    • Unknown - no known functional classification
  • Molecule Type: Sample used to find this variant
    • Genomic - variant discovered using a genomic template
    • cDNA - variant discovered using a cDNA template
    • Unknown - sample type not known
  • Unusual Conditions (UCSC): UCSC checks for several anomalies that may indicate a problem with the mapping, and reports them in the Annotations section of the SNP details page if found:
    • AlleleFreqSumNot1 - Allele frequencies do not sum to 1.0 (+-0.01). This SNP's allele frequency data are probably incomplete.
    • DuplicateObserved, MixedObserved - Multiple distinct insertion SNPs have been mapped to this location, with either the same inserted sequence (Duplicate) or different inserted sequence (Mixed).
    • FlankMismatchGenomeEqual, FlankMismatchGenomeLonger, FlankMismatchGenomeShorter - NCBI's alignment of the flanking sequences had at least one mismatch or gap near the mapped SNP position. (UCSC's re-alignment of flanking sequences to the genome may be informative.)
    • MultipleAlignments - This SNP's flanking sequences align to more than one location in the reference assembly.
    • NamedDeletionZeroSpan - A deletion (from the genome) was observed but the annotation spans 0 bases. (UCSC's re-alignment of flanking sequences to the genome may be informative.)
    • NamedInsertionNonzeroSpan - An insertion (into the genome) was observed but the annotation spans more than 0 bases. (UCSC's re-alignment of flanking sequences to the genome may be informative.)
    • NonIntegerChromCount - At least one allele frequency corresponds to a non-integer (+-0.010000) count of chromosomes on which the allele was observed. The reported total sample count for this SNP is probably incorrect.
    • ObservedContainsIupac - At least one observed allele from dbSNP contains an IUPAC ambiguous base (e.g., R, Y, N).
    • ObservedMismatch - UCSC reference allele does not match any observed allele from dbSNP. This is tested only for SNPs whose class is single, in-del, insertion, deletion, mnp or mixed.
    • ObservedTooLong - Observed allele not given (length too long).
    • ObservedWrongFormat - Observed allele(s) from dbSNP have unexpected format for the given class.
    • RefAlleleMismatch - The reference allele from dbSNP does not match the UCSC reference allele, i.e., the bases in the mapped position range.
    • RefAlleleRevComp - The reference allele from dbSNP matches the reverse complement of the UCSC reference allele.
    • SingleClassLongerSpan - All observed alleles are single-base, but the annotation spans more than 1 base. (UCSC's re-alignment of flanking sequences to the genome may be informative.)
    • SingleClassZeroSpan - All observed alleles are single-base, but the annotation spans 0 bases. (UCSC's re-alignment of flanking sequences to the genome may be informative.)
    Another condition, which does not necessarily imply any problem, is noted:
    • SingleClassTriAllelic, SingleClassQuadAllelic - Class is single and three or four different bases have been observed (usually there are only two).
  • Miscellaneous Attributes (dbSNP): several properties extracted from dbSNP's SNP_bitfield table (see dbSNP_BitField_v5.pdf for details)
    • Clinically Associated - SNP is in OMIM/OMIA and/or at least one submitter is a Locus-Specific Database. This does not necessarily imply that the variant causes any disease, only that it has been observed in clinical studies.
    • Appears in OMIM/OMIA - SNP is mentioned in Online Mendelian Inheritance in Man for human SNPs, or Online Mendelian Inheritance in Animals for non-human animal SNPs. Some of these SNPs are quite common, others are known to cause disease; see OMIM/OMIA for more information.
    • Has Microattribution/Third-Party Annotation - At least one of the SNP's submitters studied this SNP in a biomedical setting, but is not a Locus-Specific Database or OMIM/OMIA.
    • Submitted by Locus-Specific Database - At least one of the SNP's submitters is associated with a database of variants associated with a particular gene. These variants may or may not be known to be causative.
    • MAF >= 5% in Some Population - Minor Allele Frequency is at least 5% in at least one population assayed.
    • MAF >= 5% in All Populations - Minor Allele Frequency is at least 5% in all populations assayed.
    • Genotype Conflict - Quality check: different genotypes have been submitted for the same individual.
    • Ref SNP Cluster has Non-overlapping Alleles - Quality check: this reference SNP was clustered from submitted SNPs with non-overlapping sets of observed alleles.
    • Some Assembly's Allele Does Not Match Observed - Quality check: at least one assembly mapped by dbSNP has an allele at the mapped position that is not present in this SNP's observed alleles.
Several other properties do not have coloring options, but do have some filtering options:
  • Average heterozygosity: Calculated by dbSNP as described here
    • Average heterozygosity should not exceed 0.5 for bi-allelic single-base substitutions.
  • Weight: Alignment quality assigned by dbSNP
    • Weight can be 0, 1, 2, 3 or 10.
    • Weight = 1 are the highest quality alignments.
    • Weight = 0 and weight = 10 are excluded from the data set.
    • A filter on maximum weight value is supported, which defaults to 1 on all tracks except the Mult. SNPs track, which defaults to 3.
    • Note: UCSC has modified the weight of each SNP that has a single mapping to the same pseudoautosomal region (PAR) on both chrX and chrY, from 3 to 1. dbSNP agrees that the weight should be 1 and will change its pipeline to detect that case and assign a weight of 1 in the future.
      The Y chromosome in this assembly contains two pseudoautosomal regions (PARs) that were taken from the corresponding regions in the X chromosome and are exact duplicates:
      chrY:10001-2649520 and chrY:59034050-59363566
      chrX:60001-2699520 and chrX:154931044-155260560
  • Submitter handles: These are short, single-word identifiers of labs or consortia that submitted SNPs that were clustered into this reference SNP by dbSNP (e.g., 1000GENOMES, ENSEMBL, KWOK). Some SNPs have been observed by many different submitters, and some by only a single submitter (although that single submitter may have tested a large number of samples).
  • AlleleFrequencies: Some submissions to dbSNP include allele frequencies and the study's sample size (i.e., the number of distinct chromosomes, which is two times the number of individuals assayed, a.k.a. 2N). dbSNP combines all available frequencies and counts from submitted SNPs that are clustered together into a reference SNP.

You can configure this track such that the details page displays the function and coding differences relative to particular gene sets. Choose the gene sets from the list on the SNP configuration page displayed beneath this heading: On details page, show function and coding differences relative to. When one or more gene tracks are selected, the SNP details page lists all genes that the SNP hits (or is close to), with the same keywords used in the function category. The function usually agrees with NCBI's function, except when NCBI's functional annotation is relative to an XM_* predicted RefSeq (not included in the UCSC Genome Browser's RefSeq Genes track) and/or UCSC's functional annotation is relative to a transcript that is not in RefSeq.

Insertions/Deletions

dbSNP uses a class called 'in-del'. We compare the length of the reference allele to the length(s) of observed alleles; if the reference allele is shorter than all other observed alleles, we change 'in-del' to 'insertion'. Likewise, if the reference allele is longer than all other observed alleles, we change 'in-del' to 'deletion'.

UCSC Re-alignment of flanking sequences

dbSNP determines the genomic locations of SNPs by aligning their flanking sequences to the genome. UCSC displays SNPs in the locations determined by dbSNP, but does not have access to the alignments on which dbSNP based its mappings. Instead, UCSC re-aligns the flanking sequences to the neighboring genomic sequence for display on SNP details pages. While the recomputed alignments may differ from dbSNP's alignments, they often are informative when UCSC has annotated an unusual condition.

Non-repetitive genomic sequence is shown in upper case like the flanking sequence, and a "|" indicates each match between genomic and flanking bases. Repetitive genomic sequence (annotated by RepeatMasker and/or the Tandem Repeats Finder with period <= 12) is shown in lower case, and matching bases are indicated by a "+".

Data Sources and Methods

The data that comprise this track were extracted from database dump files and headers of fasta files downloaded from NCBI. The database dump files were downloaded from ftp://ftp.ncbi.nih.gov/snp/organisms/ organism_tax_id/database/ (e.g., for Human, organism_tax_id = human_9606). The fasta files were downloaded from ftp://ftp.ncbi.nih.gov/snp/organisms/ organism_tax_id/rs_fasta/

  • Coordinates, orientation, location type and dbSNP reference allele data were obtained from b135_SNPContigLoc_37_3.bcp.gz and b135_ContigInfo_37_3.bcp.gz.
  • b135_SNPMapInfo_37_3.bcp.gz provided the alignment weights.
  • Functional classification was obtained from b135_SNPContigLocusId_37_3.bcp.gz. The internal database representation uses dbSNP's function terms, but for display in SNP details pages, these are translated into Sequence Ontology terms.
  • Validation status and heterozygosity were obtained from SNP.bcp.gz.
  • SNPAlleleFreq.bcp.gz and ../shared/Allele.bcp.gz provided allele frequencies. For the human assembly, allele frequencies were also taken from SNPAlleleFreq_TGP.bcp.gz .
  • Submitter handles were extracted from Batch.bcp.gz, SubSNP.bcp.gz and SNPSubSNPLink.bcp.gz.
  • SNP_bitfield.bcp.gz provided miscellaneous properties annotated by dbSNP, such as clinically-associated. See the document dbSNP_BitField_v5.pdf for details.
  • The header lines in the rs_fasta files were used for molecule type, class and observed polymorphism.

Orthologous Alleles (human assemblies only)

For the human assembly, we provide a related table that contains orthologous alleles in the chimpanzee, orangutan and rhesus macaque reference genome assemblies. We use our liftOver utility to identify the orthologous alleles. The candidate human SNPs are a filtered list that meet the criteria:

  • class = 'single'
  • mapped position in the human reference genome is one base long
  • aligned to only one location in the human reference genome
  • not aligned to a chrN_random chrom
  • biallelic (not tri- or quad-allelic)
In some cases the orthologous allele is unknown; these are set to 'N'. If a lift was not possible, we set the orthologous allele to '?' and the orthologous start and end position to 0 (zero).

Masked FASTA Files (human assemblies only)

FASTA files that have been modified to use IUPAC ambiguous nucleotide characters at each base covered by a single-base substitution are available for download here. Note that only single-base substitutions (no insertions or deletions) were used to mask the sequence, and these were filtered to exlcude problematic SNPs.

References

Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2001 Jan 1;29(1):308-11.