## Description

This track contains information about single nucleotide polymorphisms and small insertions and deletions (indels) — collectively Simple Nucleotide Polymorphisms — from dbSNP build 131, available from ftp.ncbi.nih.gov/snp.

## 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.

The configuration categories reflect the following definitions (not all categories apply to this assembly):

- 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 variation in counts of short tandem repeats
  - Named - the observed allele from dbSNP is given as a text name
  - No Variation - no variation asserted for sequence
  - Mixed - the cluster contains submissions from multiple classes
  - Multiple Nucleotide Polymorphism - alleles of the same length, length > 1, and from set of {A,T,C,G}
  - 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: Predicted functional role (each variant may have more than one functional role)
  - Locus Region - variation within 2000 bases of gene, but not in transcript (`near-gene-3`, `near-gene-5`)
  - Coding - Synonymous - no change in peptide for allele with respect to reference assembly (`coding-synon`)
  - Coding - Non-Synonymous - change in peptide for allele with respect to reference assembly (`nonsense`, `missense`, `frameshift`, `cds-indel`, `coding-synonymy-unknown`)
  - Untranslated - variation in transcript, but not in coding region interval (`untranslated-3`, `untranslated-5`)
  - Intron - variation in intron, but not in first two or last two bases of intron
  - Splice Site - variation in first two or last two bases of intron (`splice-3`, `splice-5`)
  - 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
- 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 3.

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, but can sometimes give a bit more detail (e.g. more detail about how close a near-gene SNP is to a nearby gene).

## 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 Annotations

UCSC checks for several unusual conditions that may indicate a problem with the mapping, and reports them in the Annotations section if found:

- The dbSNP reference allele is not the same as the UCSC reference allele, i.e. the bases in the mapped position range.
- Class is single, in-del, mnp or mixed and the UCSC reference allele does not match any observed allele.
- In NCBI's alignment of flanking sequences to the genome, part of the flanking sequence around the SNP does not align to the genome.
- Class is single, but the size of the mapped SNP is not one base.
- Class is named and indicates an insertion or deletion, but the size of the mapped SNP implies otherwise.
- Class is single and the format of observed alleles is unexpected.
- The length of the observed allele(s) is not available because it is too long.
- Multiple distinct insertion SNPs have been mapped to this location.
- At least one observed allele contains an ambiguous IUPAC base (e.g. R, Y, N).

Another condition, which does not necessarily imply any problem, is noted:

- Class is single and SNP is tri-allelic or quad-allelic.

## 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

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 b131_SNPContigLoc_37_1.bcp.gz and b131_ContigInfo_37_1.bcp.gz.
- b131_SNPMapInfo_37_1.bcp.gz provided the alignment weights.
- Functional classification was obtained from b131_SNPContigLocusId_37_1.bcp.gz.
- Validation status and heterozygosity were obtained from SNP.bcp.gz.
- The header lines in the rs_fasta files were used for molecule type, class and observed polymorphism.

## Orthologous Alleles (human assemblies only)

Beginning with the March 2006 human assembly, we provide a related table that contains orthologous alleles in the chimpanzee and rhesus macaque assemblies. Beginning with dbSNP build 129, the orangutan assembly is also included. We use our liftOver utility to identify the orthologous alleles. The candidate human SNPs are a filtered list that meet the criteria:

- class = 'single'
- chromEnd = chromStart + 1
- align to just one location
- are not aligned to a chrN_random chrom
- are 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.