My-Local-SNP-Checker

Cross-reference your 23andMe raw data with ClinVar's SNP data locally:

This tool cross-references RSIDs in your direct-to-consumer (DTC) raw data file (e.g., 23andMe) against ClinVar. It runs entirely on your computer and never uploads your data.

• Input: 23andMe/Ancestry/MyHeritage TXT or single-sample VCF
• Reference: ClinVar variant_summary.txt.gz (and optionally ClinVar VCF) downloaded once, cached locally
• Output: A human-readable report saved next to your genotype file

Educational use only; not a clinical test. Consult clinical genetics for medical decisions.

Features

• Gene filtering: Choose one or more genes to focus on.
• ClinicalSignificance modes:
  • pathogenic (default) — includes "pathogenic" and "likely pathogenic" via substring match
  • risk_trait — includes risk/trait terms (risk factor, association, protective, affects, drug response, confers sensitivity/resistance)
  • broad — union of pathogenic + risk_trait
  • custom — supply your own terms with --clinsig-terms "term1,term2"
• Allele-aware check (TXT inputs): Uses ClinVar VCF to test if your bases include the ALT allele(s) for matched RSIDs
• Privacy: Your genotype file is read locally only

Quick start

1. Ensure Python 3 is installed (macOS usually has it).

2. Run the reproductive genetic carrier panel (pathogenic):

python3 rsid_clinvar_checker.py \
  --genotype "/absolute/path/to/your_raw.txt" \
  --genes HBA1,HBA2,HBB,ASPA,CFTR,DLD,ELP1,ABCC8,FANCC,FMR1,GBA,G6PC,TMEM216,BCKDHB,MCOL1,NEB,SMPD1,SMN1,SMN2,HEXA,PCDH15,CLRN1,FKTN \
  --mode pathogenic

3. For allele-aware calls (TXT inputs only):

python3 rsid_clinvar_checker.py \
  --genotype "/absolute/path/to/your_raw.txt" \
  --genes HBA1,HBA2,HBB,ASPA,CFTR,DLD,ELP1,ABCC8,FANCC,FMR1,GBA,G6PC,TMEM216,BCKDHB,MCOL1,NEB,SMPD1,SMN1,SMN2,HEXA,PCDH15,CLRN1,FKTN \
  --mode pathogenic \
  --allele-aware

4. Custom ClinicalSignificance terms:

python3 rsid_clinvar_checker.py \
  --genotype "/absolute/path/to/your_raw.txt" \
  --genes APOE,LCT \
  --mode custom \
  --clinsig-terms "risk factor,association,drug response"

Interpreting results

• The report prints to the terminal and saves as rsid_clinvar_report.txt next to your genotype file.
• "Overlaps found" means your file contains the listed RSIDs that ClinVar classifies with the selected terms.
• With --allele-aware (TXT inputs), the tool reports if your bases include the specific ALT allele(s) for those RSIDs.
• Important: RSIDs can tag multiple alleles. An RSID match alone does not confirm the specific allele.

Common RSIDs for sanity checks (read-only)

grep -E '^(rs334|rs113993960|rs28929474|rs1050828|rs1800562)[[:space:]]' \
  "/absolute/path/to/your_raw.txt" | head

• If lines appear, your chip likely covers some positive-control variants.

Notes and limitations

• Many pathogenic variants lack rsIDs or are not on consumer SNP arrays; a negative screen does not rule out disease.
• ClinVar classifications change over time; re-run periodically to use the latest reference.
• For medical decisions, use clinical-grade testing and consult a clinician.

License

MIT