ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5074+1G>A (rs80358053)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031210 SCV000244381 pathogenic Breast-ovarian cancer, familial 1 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on posterior probability = 1
Invitae RCV000048764 SCV000076777 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-04 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 16 of the BRCA1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in a family affected with triple-negative breast cancer (PMID: 27553291). This variant is also known as IVS17+1G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 37629). Multifactorial likelihood analyses based on genetic evidence such as family history, co-segregation with disease, and co-occurrence with pathogenic variants predict that this variant is likely deleterious (PMID: 17924331, 21990134). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131833 SCV000186888 pathogenic Hereditary cancer-predisposing syndrome 2017-10-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity,Other strong data supporting pathogenic classification
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031210 SCV000296376 pathogenic Breast-ovarian cancer, familial 1 2015-08-21 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031210 SCV000326131 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000481404 SCV000566057 pathogenic not provided 2016-08-02 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.5074+1G>A or IVS16+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 16 of the BRCA1 gene. The variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant, also known as 5193+1G>A using alternate nomenclature, has been strongly predicted by Lindor et al. (2012) to be deleterious based on tumor pathology, clinical histories, and family studies. We therefore consider this variant to be pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048764 SCV000591570 pathogenic Hereditary breast and ovarian cancer syndrome 2015-05-06 criteria provided, single submitter clinical testing
Color RCV000131833 SCV000683247 pathogenic Hereditary cancer-predisposing syndrome 2015-10-07 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031210 SCV000053810 pathogenic Breast-ovarian cancer, familial 1 2012-03-05 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031210 SCV000145288 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing

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