ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4485-1G>A (rs80358189)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000112343 SCV000221033 pathogenic Breast-ovarian cancer, familial 1 2015-01-15 criteria provided, single submitter literature only
GeneDx RCV000235386 SCV000293181 pathogenic not provided 2015-09-28 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4485-1G>A or IVS13-1G>A and consists of a G>A nucleotide substitution at the -1 position of intron 13 of the BRCA1 gene. This variant destroys a canonical splice acceptor 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 BRCA1 c.4604-1G>A or IVS14-1G>A by alternative nomenclature, has been reported in at least two hereditary breast/ovarian cancer families (Liede 2002). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000112343 SCV000296365 pathogenic Breast-ovarian cancer, familial 1 2015-07-15 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112343 SCV000325984 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000496695 SCV000591521 pathogenic Hereditary breast and ovarian cancer syndrome 2014-11-18 criteria provided, single submitter clinical testing
Color RCV000580034 SCV000683190 likely pathogenic Hereditary cancer-predisposing syndrome 2018-07-29 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000496695 SCV000699153 pathogenic Hereditary breast and ovarian cancer syndrome 2017-01-06 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.4485-1G>A variant involves the alteration of a non-conserved intronic nucleotide, at a location known to affect splicing, which 4/5 splice prediction tools predict a potential affect on splicing and ESE finder predicts alterations to ESE binding, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 2/118768 (1/59382), which does not exceed the estimated maximal expected allele frequency for a pathogenic BRCA1 variant of 1/1000. However, these observations need to be cautiously considered due the cohort harboring individuals that could have a BRCA1 phenotype. Multiple publications cite the variant in affected individuals, in particular, individuals from Pakistan and has been indicated to be a founder mutation. In addition, multiple clinical diagnostic laboratories classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000762999 SCV000893444 pathogenic Familial cancer of breast; Breast-ovarian cancer, familial 1; Pancreatic cancer 4; FANCONI ANEMIA, COMPLEMENTATION GROUP S 2018-10-31 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112343 SCV000145102 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496695 SCV000587402 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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