What a single annotated pathogenic call looks like in Baseshift, end to end — identity, HGVS, ACMG/AMP verdict, criteria, evidence, sources.
chr17 · 7,674,220 · G→A
rs28934576 — a well-characterized Li-Fraumeni syndrome founder allele.
The same record (chr17 7674220 rs28934576 G A) is included in the bundled sample-data.vcf, so reviewers can verify the annotation end to end against a known pathogenic ClinVar call without uploading their own data.
Genomic — chr17:g.7674220G>A
Coding (cDNA) — NM_000546.6:c.524G>A
Protein — p.Arg175His (p.R175H)
Genomic g. notation is computed at parse time from chr:pos:ref:alt in vcf-parser.js; the cDNA/protein notation below it is what the AI annotation step provides per variant when transcript context is available.
ClinVar significance — Pathogenic · Baseshift ACMG verdict — Pathogenic
ACMG criteria codes triggered for this variant:
Verdict, criteria string, and plain-language summary are written to variants.acmg_verdict, acmg_criteria, and acmg_summary by lib/acmg-classifier.js, then surfaced as a color-coded badge in every report template and as a sortable column in the dashboard.
One row per triggered ACMG criterion. Codes link to the row below; strengths follow the ACMG/AMP 2015 framework (Strong / Moderate / Supporting).
| Code | Strength | Evidence |
|---|---|---|
| PS1 | Strong | Same amino-acid change (Arg175His) as an established pathogenic variant in TP53, reported in ClinVar with multiple submitters and no conflicting interpretations. |
| PM1 | Moderate | Located in the TP53 DNA-binding domain, a well-characterized mutational hotspot where missense changes at codon 175 are recurrent in somatic and germline tumor cohorts. |
| PM2 | Moderate | Absent from gnomAD v4 population database (allele frequency not observed in >800k individuals); consistent with a rare, disease-causing variant. |
| PP3 | Supporting | Multiple computational predictors support a damaging effect — SIFT: deleterious, PolyPhen-2: probably damaging, CADD: >30. Concordance across in-silico tools is required for PP3 to fire. |
| PP5 | Supporting | Reputable source (ClinVar) reports Pathogenic significance with multiple submitters and review status of at least 2 stars, without conflict. |
frequency_cache).The combinator (Strong ×1, Moderate ×2, Supporting ×2) crosses the Pathogenic threshold under the ACMG/AMP 2015 combining rules. The rule-based verdict matches the expert-curated ClinVar significance for this allele.
Upload a VCF and get the same field set — HGVS notation, ACMG verdict, criteria codes, ClinVar significance, gnomAD frequency, OMIM condition — rendered into a downloadable clinical PDF. 5 free samples, no contract.