# ClinVar — NCBI Clinical Variant Database ## Overview ClinVar is a public repository of clinical interpretations of genomic variants, operated by NCBI/NIH since 2013. It aggregates variant-phenotype relationships submitted by clinical laboratories, research groups, and expert panels worldwide, and assigns each variant a clinical significance classification based on submitted evidence. Variants are identified using HGVS notation and are increasingly assigned [[VRS]] globally unique computed identifiers for cross-system deduplication. [[ClinGen]] expert panels submit curated variant classifications that receive the highest evidence tier and take precedence over individual laboratory submissions. ## Content and Classification - Clinical significance is classified on a five-tier scale: Pathogenic, Likely pathogenic, Uncertain significance (VUS), Likely benign, and Benign. - Evidence quality is rated on a one-to-four star scale reflecting the number and concordance of submissions, with [[ClinGen]] expert panel reviews at the top tier. - Variant types include single nucleotide variants, indels, copy number variants, and structural variants. - Disease associations are coded using [[OMIM]] MIM numbers, MedGen identifiers, [[MONDO]], and [[HPO]] terms. ## Connections - Operated by: NCBI / NIH - Expert curation by: [[ClinGen]] - Cross-references: [[dbSNP]], [[OMIM]], [[HPO]], [[MONDO]] - Uses: [[VCF]], [[VRS]] ## Resources - https://www.ncbi.nlm.nih.gov/clinvar/ - https://www.ncbi.nlm.nih.gov/books/NBK174587/ (NCBI Handbook, ClinVar) - https://clinicalgenome.org (ClinGen, expert variant curation) - https://gnomad.broadinstitute.org (gnomAD, population allele frequencies) - https://vrs.ga4gh.org (VRS, globally unique variant identifiers)