bio-clinical-databases-clinvar-lookup

REST API Queries

Goal: Retrieve ClinVar pathogenicity classifications and disease associations for variants via REST API.

Approach: Query NCBI E-utilities endpoints with variant IDs, gene symbols, or HGVS notation and parse JSON responses.

"Look up this variant in ClinVar" → Query ClinVar database for clinical significance, review status, and disease associations.

• Python: requests.get() against NCBI E-utilities (requests)
• CLI: esearch/efetch (Entrez Direct)

Local ClinVar VCF

Goal: Query variants against a local ClinVar VCF for fast, offline pathogenicity lookups.

Approach: Download the ClinVar VCF from NCBI FTP, then query by genomic coordinates using cyvcf2 or bcftools.

Clinical Significance Categories

Value	Interpretation
Pathogenic	Disease-causing
Likely_pathogenic	Probably disease-causing
Uncertain_significance	VUS - unknown
Likely_benign	Probably not disease-causing
Benign	Not disease-causing
Conflicting_interpretations	Multiple labs disagree