ClinVar Lookup
REST API Queries
Query by Variant ID
import requests
def query_clinvar_by_id(variation_id):
'''Query ClinVar by variation ID'''
url = f'https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi'
params = {
'db': 'clinvar',
'id': variation_id,
'retmode': 'json'
}
response = requests.get(url, params=params)
return response.json()
result = query_clinvar_by_id('16609')
Search by Gene
def search_clinvar_gene(gene_symbol, pathogenic_only=False):
'''Search ClinVar for variants in a gene'''
url = 'https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi'
term = f'{gene_symbol}[gene]'
if pathogenic_only:
term += ' AND pathogenic[clinical_significance]'
params = {
'db': 'clinvar',
'term': term,
'retmax': 500,
'retmode': 'json'
}
response = requests.get(url, params=params)
return response.json()
Search by HGVS
def search_clinvar_hgvs(hgvs):
'''Search ClinVar by HGVS notation'''
url = 'https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi'
params = {
'db': 'clinvar',
'term': f'{hgvs}[variant name]',
'retmode': 'json'
}
response = requests.get(url, params=params)
return response.json()
Local ClinVar VCF
Download ClinVar VCF
# GRCh38
wget https://ftp.ncbi.nlm.nih.gov/pub/clinvar/vcf_GRCh38/clinvar.vcf.gz
wget https://ftp.ncbi.nlm.nih.gov/pub/clinvar/vcf_GRCh38/clinvar.vcf.gz.tbi
# GRCh37
wget https://ftp.ncbi.nlm.nih.gov/pub/clinvar/vcf_GRCh37/clinvar.vcf.gz
Query Local ClinVar with cyvcf2
from cyvcf2 import VCF
clinvar = VCF('clinvar.vcf.gz')
def lookup_variant(chrom, pos, ref, alt):
'''Look up variant in local ClinVar VCF'''
region = f'{chrom}:{pos}-{pos}'
for variant in clinvar(region):
if variant.REF == ref and alt in variant.ALT:
return {
'clnsig': variant.INFO.get('CLNSIG'),
'clnrevstat': variant.INFO.get('CLNREVSTAT'),
'clndn': variant.INFO.get('CLNDN'),
'clnvc': variant.INFO.get('CLNVC')
}
return None
result = lookup_variant('7', 140453136, 'A', 'T')
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 |
Review Status Stars
| Stars |
Review Status |
| 4 |
Practice guideline |
| 3 |
Expert panel reviewed |
| 2 |
Multiple submitters, criteria provided |
| 1 |
Single submitter, criteria provided |
| 0 |
No assertion criteria |
Parse ClinVar INFO Fields
def parse_clinvar_significance(clnsig):
'''Parse ClinVar CLNSIG field'''
pathogenic_terms = ['Pathogenic', 'Likely_pathogenic']
benign_terms = ['Benign', 'Likely_benign']
if any(term in clnsig for term in pathogenic_terms):
return 'pathogenic'
elif any(term in clnsig for term in benign_terms):
return 'benign'
elif 'Conflicting' in clnsig:
return 'conflicting'
else:
return 'vus'
Batch Annotation with bcftools
# Annotate VCF with ClinVar
bcftools annotate \
-a clinvar.vcf.gz \
-c INFO/CLNSIG,INFO/CLNREVSTAT,INFO/CLNDN \
input.vcf.gz \
-o annotated.vcf.gz
Related Skills
- myvariant-queries - Aggregated queries including ClinVar
- variant-prioritization - Filter by ClinVar significance
- variant-calling/clinical-interpretation - ACMG guidelines
tools-only