ClinVar: public archive of relationships among sequence variation and human phenotype

Abstract

ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/) provides a freely available archive of reports of relationships among medically important variants and phenotypes. ClinVar accessions submissions reporting human variation, interpretations of the relationship of that variation to human health and the evidence supporting each interpretation. The database is tightly coupled with dbSNP and dbVar, which maintain information about the location of variation on human assemblies. ClinVar is also based on the phenotypic descriptions maintained in MedGen (http://www.ncbi.nlm.nih.gov/medgen). Each ClinVar record represents the submitter, the variation and the phenotype, i.e. the unit that is assigned an accession of the format SCV000000000.0. The submitter can update the submission at any time, in which case a new version is assigned. To facilitate evaluation of the medical importance of each variant, ClinVar aggregates submissions with the same variation/phenotype combination, adds value from other NCBI databases, assigns a distinct accession of the format RCV000000000.0 and reports if there are conflicting clinical interpretations. Data in ClinVar are available in multiple formats, including html, download as XML, VCF or tab-delimited subsets. Data from ClinVar are provided as annotation tracks on genomic RefSeqs and are used in tools such as Variation Reporter (http://www.ncbi.nlm.nih.gov/variation/tools/reporter), which reports what is known about variation based on user-supplied locations.

Figure 1.

Tabular display of query results with filters applied. In this example http://www.ncbi.nlm.nih.gov/clinvar?term=rasopathy&cmd=DetailsSearch), the query ‘rasopathy’ returned more than 225 results, but when the selection of ‘Pathogenic’ was applied, the number of results was reduced to 127. The number of records in each category is reported. The check mark to the left of the filter name as well as the report at the top of the page are used to remind the user about the filters that have been applied. These filters can be removed using the ‘Clear’ option. To see the details of any record that was found, click on ‘See details’. To alter the display and change the sorting order, open the ‘Display Settings’ menu above the table.

Figure 2.

Representative display of an RCV accession RCV000033555.3 generated by aggregating information in two submissions (SCV000057460 and SCV000058286). The information above the tabbed section includes information from the submitters and values added by NCBI (e.g. GeneIDs, Mendelian Inheritance in Man (MIM) numbers, rs numbers and links to MedGen). The information in the ‘Clinical Assertions’ and ‘Evidence’ tabs are organized by what each submitter contributed and are extracted from the SCV records.