ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.548-9delA (rs273902774)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159865 SCV000209914 likely benign not specified 2018-01-30 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000200830 SCV000253518 benign Hereditary breast and ovarian cancer syndrome 2017-12-26 criteria provided, single submitter clinical testing
Counsyl RCV000031259 SCV000489382 likely benign Breast-ovarian cancer, familial 1 2016-09-27 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588280 SCV000699265 likely benign not provided 2017-02-15 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.548-9delA variant involves the deletion of a non-conserved intronic nucleotide in a stretch of 3 adenines that is 9bp away from the closest intron-exon junction. One in silico tool (Mutation Taster) predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing, and ESE finder predicts no significant changes in ESEs. However, these predictions have yet to be confirmed by functional studies. This variant was found in ExAC, a large control database, in 3/120290 control chromosomes at a frequency of 0.0000249, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). However, all 3 ExAC occurrences were from individuals of African ancestry (3/9952; frequency 0.0003). Additionally, in gnomAD, another large control database containing ExAC data and additional exome and genome data, the variant was found in 9/282072 control chromosomes at a frequency of 0.0000249. All 9 gnomAD occurrences were from individuals of African ancestry (9/25784; frequency of 0.00035). Given the ExAC and gnomAD data, the variant appears to be specific to African populations and suggests the variant is likely a rare, ethnically-specific polymorphism. Two publications cite the variant (one in a Nigerian BrC patient population, the other from individuals screened for BRCA mutation(s) by Myriad, ethnicity not specified), but neither provides information/data on co-segregation with disease or functional analyses. Both studies classify the variant as uncertain. Multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as a likely benign variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000588280 SCV000702258 uncertain significance not provided 2016-10-03 criteria provided, single submitter clinical testing
Color RCV000776096 SCV000910902 likely benign Hereditary cancer-predisposing syndrome 2016-04-07 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031259 SCV000053863 benign Breast-ovarian cancer, familial 1 2009-11-04 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031259 SCV000145626 uncertain significance Breast-ovarian cancer, familial 1 2002-06-20 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735565 SCV000863703 benign Breast and/or ovarian cancer no assertion criteria provided clinical testing

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