Classification
ACMG/AMP 2015 classification with Bayesian point-based framework (Tavtigian 2018/2020)
19 of 28 ACMG criteria automated
BayesDel_noAF with ClinGen SVI-calibrated thresholds for PP3/BP4 (Pejaver 2022)
SpliceAI integration for PP3_splice with PVS1 double-counting prevention
ClinVar override logic with review star quality filtering
Gene-specific VCEP threshold support
Reference Databases
gnomAD v4.1 (759M variants, 807K individuals)
gnomAD Constraint v4.1 (18.2K genes)
ClinVar 2025-01
dbNSFP 4.9c
SpliceAI precomputed (Ensembl MANE Release 113)
HPO gene-phenotype associations
ClinGen dosage sensitivity
Ensembl VEP Release 113 with local offline cache
Phenotype Matching
Lin semantic similarity with HPO ontology graph
Five-tier clinical priority system
Gene-level deduplication and aggregation
Automatic HPO term extraction from free-text clinical descriptions
Screening
Seven-component scoring algorithm (constraint, deleteriousness, phenotype, dosage, consequence, compound het, age relevance)
Six screening modes (diagnostic, neonatal, pediatric, proactive adult, carrier, pharmacogenomics)
Age-aware prioritization with curated gene lists
Clinical boosts for ethnicity, family history, sex-linked inheritance, consanguinity, pregnancy
Four-tier priority ranking with clinical actionability labels
AI Clinical Assistant
Conversational variant analysis with natural language database queries
Biomedical literature search (1M+ publications, local PubMed mirror)
Four-level adaptive clinical interpretation generation
PDF and DOCX report export with Helix Insight branding
Genomics-aware visualization suggestions
On-premise LLM inference within EU infrastructure
Infrastructure
EU-based processing (Helsinki, Finland)
All databases stored and queried locally
Zero external API calls during variant processing
GDPR-compliant data handling
DuckDB-based analytical pipeline