Variant Evidence

Variant And Gene Evidence

Use this skill when the user asks about a specific rsID, allele, gene, genomic region, observed genotype, absence/reference claim, or whether the user's own Active Genome Index supports a claim.

Goal

Answer with the smallest evidence packet needed. Use sample support and callability checks when the claim requires them.

Run genomi.describe_context first if the Active Genome Index is unknown. If an active Active Genome Index exists, use it for sample-specific lookup. With public-only context, answer from public/source evidence or ask the user for a file only when personal evidence is required.

Use variant.resolve as the umbrella first lookup when the user's target is an rsID, coordinate, exact allele, locus, region, or mixed text. It resolves flexible input, checks the Active Genome Index, gathers existing deterministic ClinVar/population/reviewed-source facts, and can search explicitly selected accessible Active Genome Index records with agi_id or include_known_active_genome_indexes.

Convention: See skills/conventions/evidence-quality.md. Convention: See skills/_output-rules.md.

Contract

Contract:

• Personal variant claims are grounded in the selected Active Genome Index.
• Public-only variant answers are clearly marked public-only.
• Absence/reference claims require callability.
• Positive allele claims use genotype support when answer confidence matters.
• Medical meaning beyond static rows uses Journal source-review memory.

Cross-Capability Synthesis

A scope-limited result from this capability is not a final user-facing answer when other Genomi capabilities can contribute orthogonal evidence to the same question. Returning "cannot answer" while applicable capabilities remain unexamined is a host-agent failure mode.

Tools

active_genome_index.classify_genotype_support

Classify whether one exact allele has enough sample support to be used in a personal interpretation.

Use when: A user-specific interpretation depends on whether one exact allele is actually supported by Active Genome Index genotype/QC evidence.

Why necessary: A reported variant match still needs depth, genotype quality, and allele support before user-specific wording is justified.

Example prompts: Does this exact allele have enough support in my Active Genome Index?

Result semantics: Returns support_status and evidence_class; the host agent decides whether weak or missing support is a gap.

active_genome_index.classify_region_callability

Classify whether a region can support reference or absence claims.

Use when: A negative, reference, absent-marker, or no-variant claim depends on whether the region was callable.

Why necessary: Absence claims require callability; a missing variant in a poorly covered region is not evidence of absence.

Example prompts: Can this region support saying a variant was absent?

Result semantics: Returns callability_status and support for negative/reference wording; the host agent writes the claim.

variant.gather_allele_context

Gather existing sample, static, population, and reviewed research evidence for one allele.

Use when: The agent needs a consolidated context pack for one exact allele before interpreting or reporting it.

Why necessary: Variant reports need sample, static, population, and reviewed-research evidence gathered without recomputing unrelated evidence.

Result semantics: Combines stored sample/static/population/research evidence; missing sections are facts for the agent to interpret.

variant.gather_gene_context

Gather existing sample, ClinVar, and reviewed research evidence for one gene.

Use when: a selected gene needs existing sample, ClinVar, and reviewed-research context before synthesis.

Why necessary: Gene-level interpretation needs gene-scoped context, which is different from one exact variant lookup.

Result semantics: Combines stored gene-scoped sample, static, and reviewed research evidence; absence of a section is not negative evidence by itself.

variant.find_gene_variants

Find passing variant records in an approved Active Genome Index that overlap managed GENCODE gene intervals for 1–10 candidate genes.

Use when: A public-evidence or phenotype investigation has produced a small, explicit candidate-gene set and the user has authorized access to the selected Active Genome Index.

Why necessary: A source VCF may not carry gene annotations. This operation resolves exact symbols through the matching-build GENCODE library, then reads only those bounded intervals through the Active Genome Index reader.

Not for: discovering or ranking candidate genes, interpreting pathogenicity, consumer genotype-array indexes that lack ref/alt variant records, or claiming that an empty interval scan rules out disease.

Result semantics: match_basis=gencode_gene_interval_overlap means only coordinate overlap. Review unresolved_genes, truncation fields, genotype support, public variant evidence, and clinical confirmation before synthesis. If the matching GENCODE library is missing, the operation returns requires_library_install; this is a blocked evidence scope, not a negative genome result.