owencqueen/cgbench_data huggingface dataset:
Gene: BRCA1 (HGNC:1100)
Evidence Code: BP4 — Original ACMG Summary
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
Caveat: As many in silico algorithms use the same or very similar input for their predictions, each algorithm cannot be counted as an independent criterion. BP4 can be used only once in any evaluation of a variant.
Gene: BRCA1 (HGNC:1100)
Evidence Code: BP4 — Supporting
Modification Type: Clarification,Gene-specific
Missense or in-frame insertion, deletion or delins variants inside a (potentially) clinically important functional domain, and no predicted impact via protein change or splicing (BayesDel no-AF score ≤ 0.15 AND SpliceAI ≤0.1).


Silent variant inside a (potentially) clinically important functional domain, if no predicted impact via splicing (SpliceAI ≤0.1).


Intronic variants outside of the native donor and acceptor splice sites (i.e. not +/- 1,2 positions) AND no predicted impact via splicing (SpliceAI ≤0.1).


As justified in the appendices, (potentially) clinically important functional domains are defined as: BRCA1 RING aa 2-101; BRCA1 coiled-coil aa 1391-1424; BRCA1 BRCT repeats aa 1650-1857. See Specifications Figure1A and Appendix J for details.
Gene: BRCA1 (HGNC:1100)
Evidence Code: BP5 — Original ACMG Summary
Variant found in a case with an alternate molecular basis for disease.
Gene: BRCA1 (HGNC:1100)
Evidence Code: BP5 — Strong
Modification Type: Gene-specific
Use ONLY to capture combined LR against pathogenicity, based on multifactorial likelihood clinical data.


BP5_VeryStrong – LR <0.00285:1


BP5_Strong  - LR <0.05:1


Not applicable for co-observation: cases with pathogenic variants in two (or more) different known breast–ovarian cancer risk genes have no specific phenotype.
Gene: BRCA1 (HGNC:1100)
Evidence Code: BP5 — Moderate
Modification Type: Gene-specific
Use ONLY to capture combined LR against pathogenicity, based on multifactorial likelihood clinical data.


BP5_Moderate - LR <0.23:1


Not applicable for co-observation: cases with pathogenic variants in two (or more) different known breast–ovarian cancer risk genes have no specific phenotype.
Gene: BRCA1 (HGNC:1100)
Evidence Code: BP5 — Supporting
Modification Type: Gene-specific
Use ONLY to capture combined LR against pathogenicity, based on multifactorial likelihood clinical data.


BP5 - LR 0.23-0.48:1


Not applicable for co-observation: cases with pathogenic variants in two (or more) different known breast–ovarian cancer risk genes have no specific phenotype.
Gene: BRCA1 (HGNC:1100)
Evidence Code: BP6 — Original ACMG Summary
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
Gene: BRCA1 (HGNC:1100)
Evidence Code: BP7 — Original ACMG Summary
A synonymous variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved.
Gene: BRCA1 (HGNC:1100)
Evidence Code: BP7 — Strong
Modification Type: General recommendation,Gene-specific
Well-established in vitro or in vivo functional studies shows no damaging effect on protein function 
as measured by effect on mRNA transcript profile – mRNA assay only.
 Apply as BP7 (RNA) for intronic and silent variants, as well as missense/in-frame variants located outside a (potentially) clinically important functional domain. See Specifications Figure1B and Appendix E for details.


As justified in the appendices, (potentially) clinically important functional domains are defined as: BRCA1 RING aa 2-101; BRCA1 coiled-coil aa 1391-1424; BRCA1 BRCT repeats aa 1650-1857. See Specifications Figure1A and Appendix J for details.
Gene: BRCA1 (HGNC:1100)
Evidence Code: BP7 — Supporting
Modification Type: Clarification,General recommendation
Silent variant inside a (potentially) clinically important functional domain, IF BP4 met.


Intronic variants located outside conserved donor or acceptor motif positions (at or beyond positions +7/-21) IF BP4 met.


See Specifications Figure1A and Appendix J for additional details.


As justified in the appendices, (potentially) clinically important functional domains are defined as: BRCA1 RING aa 2-101; BRCA1 coiled-coil aa 1391-1424; BRCA1 BRCT repeats aa 1650-1857. See Specifications Figure1A and Appendix J for details.