owencqueen/cgbench_data huggingface dataset:
Gene: BRCA1 (HGNC:1100)
Evidence Code: PP1 — Strong
Modification Type: Gene-specific
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease, as measured by a quantitative co-segregation analysis method. See Appendix I for details.


Apply weight as per Bayes Score:


PP1_Strong – LR ≥18.7:1


PP1_Very Strong – LR ≥350:1
Gene: BRCA1 (HGNC:1100)
Evidence Code: PP1 — Moderate
Modification Type: Gene-specific
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease, as measured by a quantitative co-segregation analysis method. See Appendix I for details.


Apply weight as per Bayes Score:


PP1_Moderate – LR ≥4.3:1
Gene: BRCA1 (HGNC:1100)
Evidence Code: PP1 — Supporting
Modification Type: Gene-specific
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease, as measured by a quantitative co-segregation analysis method. See Appendix I for details.


Apply weight as per Bayes Score:


PP1 - LR ≥2.08:1
Gene: BRCA1 (HGNC:1100)
Evidence Code: PP4 — Strong
Modification Type: Gene-specific
Breast cancer is very common and has a high degree of genetic heterogeneity (caused by pathogenic variants in numerous genes). Use ONLY to capture combined LR towards pathogenicity, based on multifactorial likelihood clinical data.


PP4_Strong – LR ≥18.7:1


PP4_Very Strong – LR ≥350:1


See Specifications Table7 and Appendix B for details.
Gene: BRCA1 (HGNC:1100)
Evidence Code: PP4 — Moderate
Modification Type: Gene-specific
Breast cancer is very common and has a high degree of genetic heterogeneity (caused by pathogenic variants in numerous genes). Use ONLY to capture combined LR towards pathogenicity, based on multifactorial likelihood clinical data.


PP4_Moderate – LR ≥4.3:1


See Specifications Table7 and Appendix B for details.
Gene: BRCA1 (HGNC:1100)
Evidence Code: PP4 — Supporting
Modification Type: Gene-specific
Breast cancer is very common and has a high degree of genetic heterogeneity (caused by pathogenic variants in numerous genes). Use ONLY to capture combined LR towards pathogenicity, based on multifactorial likelihood clinical data.


PP4 - LR ≥2.08:1 


See Specifications Table7 and Appendix B for details.
Gene: BRCA1 (HGNC:1100)
Evidence Code: BS4 — Strong
Modification Type: Gene-specific
Lack of segregation in affected members of a family, as measured by a quantitative co-segregation analysis method. See Appendix I for details.


Apply weight as per Bayes Score:


BS4 - LR ≤0.05:1


BS4_VeryStrong – LR ≤0.00285:1
Gene: BRCA1 (HGNC:1100)
Evidence Code: BS4 — Moderate
Modification Type: Gene-specific
Lack of segregation in affected members of a family, as measured by a quantitative co-segregation analysis method. See Appendix I for details.


Apply weight as per Bayes Score:


BS4_Moderate - LR ≤0.23:1
Gene: BRCA1 (HGNC:1100)
Evidence Code: BS4 — Supporting
Modification Type: Gene-specific
Lack of segregation in affected members of a family, as measured by a quantitative co-segregation analysis method. See Appendix I for details.


Apply weight as per Bayes Score:


BS4_Supporting  - LR ≤0.48:1
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 — 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 ≤0.48:1


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: 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_Strong (RNA) for intronic and silent variants, as well as missense/in-frame variants located outside a (potentially) clinically important functional domain. Missense variants located inside a (potentially) clinically important functional domain must meet BS3 to be eligible for BP7_Strong (RNA). 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.