# vcf2report - gbbarra

- **Event:** [Built with Claude: Life Sciences](https://cerebralvalley.ai/e/built-with-claude-life-sciences)
- **When:** Jul 7 at 12:00 PM – Jul 14 at 12:00 AM (EDT)
- **Where:** Online
- **Team:** [Gustavo Barra](https://cerebralvalley.ai/u/gbbarra)
- **GitHub:** https://github.com/gbbarra/vcf2report
- **Demo video:** https://youtu.be/QF3twmeWA2U
- **Gallery:** https://cerebralvalley.ai/e/built-with-claude-life-sciences/hackathon/gallery
- **Page:** https://cerebralvalley.ai/e/built-with-claude-life-sciences/hackathon/gallery/142

vcf2report turns a raw exome VCF + the patient's phenotype (HPO terms) into an
auditable, clinical-grade ACMG variant report — locally, offline, in seconds.

Exome interpretation today is slow and manual: an analyst hand-filters thousands of
variants across several databases and matches each candidate to the patient's
phenotype one by one. vcf2report runs the whole pipeline — parse ▸ QC ▸ annotate ▸
prioritize ▸ classify ▸ report — and returns a draft laudo for expert sign-off,
showing the full ACMG reasoning for every variant: all 28 ACMG/AMP criteria, each
with its concrete evidence value, its source (database + accession + date), and
whether the deterministic engine decided it or it is honestly deferred to
expert/model review.

What makes it different from a black-box classifier:
• Auditable — you see *why* a variant is Pathogenic; the trio/segregation criteria
  a single-proband VCF cannot support are marked N/A instead of guessed.
• Brazilian population frequencies (ABraOM/SABE) on top of gnomAD, so a variant
  absent from gnomAD but common in Brazilians is correctly dropped.
• ClinGen-calibrated AlphaMissense (PP3/BP4), deterministic PVS1 via the ClinGen
  SVI tree, and ontology-aware HPO phenotype matching (Lin/Information-Content).
• Offline gnomAD: a 29.6M-variant DuckDB/Parquet store classifies a whole exome in
  ~7 s with the VCF never leaving the machine.

Why it matters: validated against 200 real ClinVar variants (100 pathogenic /
100 benign, with ClinVar withheld from the engine), it produced 0 gross
pathogenic↔benign flips and 100% precision when decisive. It is deliberately
conservative — never dangerously wrong, and right whenever it commits — which is
exactly the property a draft-generation aid for a clinician needs.

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