ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4484+1G>A (rs80358063)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000573576 SCV000660949 pathogenic Hereditary cancer-predisposing syndrome 2017-08-18 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,Functionally-validated splicing mutation
Bioinformatics dept.,Datar Cancer Genetics Limited, India RCV000031177 SCV000584008 pathogenic Breast-ovarian cancer, familial 1 2017-07-12 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031177 SCV000145097 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031177 SCV000325974 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031177 SCV000785887 pathogenic Breast-ovarian cancer, familial 1 2017-12-29 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048572 SCV000591517 pathogenic Hereditary breast and ovarian cancer syndrome 2014-08-08 criteria provided, single submitter clinical testing
GeneDx RCV000521426 SCV000617449 pathogenic not provided 2017-05-16 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4484+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. Using alternate nomenclature, this variant has previously been published as BRCA1 4603+1G>A and BRCA1 IVS14+1G>A. This 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 has been reported in association with breast and ovarian cancer and has been shown in functional studies to result in skipping of exon 13, also known as exon 14 by alternate nomenclature (Perkowska 2003, Brozek 2008, Houdayer 2012, Juwle 2012, Steffensen 2014, Koczkowska 2016). Based on the current evidence, we consider this variant to be pathogenic.
GeneKor MSA RCV000585660 SCV000693536 pathogenic Familial cancer of breast 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV000048572 SCV000076585 pathogenic Hereditary breast and ovarian cancer syndrome 2018-03-05 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 13 of the BRCA1 gene. It is expected to disrupt mRNA 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 reported in individuals with early-onset breast cancer (PMID: 22752604), and in a family with breast and ovarian cancer (PMID: 12673801). This variant is also known as IVS14+1G>A and 4603+1G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 37596). Experimental studies have shown that this donor splice site variant leads to skipping of exon 13, which is also known as exon 14 in the literature. (PMID: 12673801, 22505045, 24667779). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000048572 SCV000605770 pathogenic Hereditary breast and ovarian cancer syndrome 2017-07-20 criteria provided, single submitter clinical testing The c.4484+1G>A variant in BRCA1 (referred to as IVS14+1G>A by some studies) has been reported in at least 3 individuals with BRCA1-associated cancers (Mannan e t al. 2016, Juwle et al. 2012, Perkowska et al. 2003). It has also been reported by other clinical laboratories in ClinVar (Variation ID# 37596) and was absent from large population studies. This variant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and has been shown to lead to skipping of exon 14 (Xiong et al. 2015, Steffensen et al. 2014), leading to a frameshift and premature termination 10 amino acids downstream of exon 13 (Houdayer et al. 201 2, Perkowska et al. 2003). Heterozygous loss of function of the BRCA1 gene is an established disease mechanism in individuals with hereditary breast and ovarian cancer (HBOC). In summary, this variant meets criteria to be classified as path ogenic for HBOC in an autosomal dominant manner based upon impact to the prote in, absence from controls and functional evidence.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048572 SCV000587400 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031177 SCV000053777 pathogenic Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.