ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4484+1G>T

dbSNP: rs80358063
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000258231 SCV000325975 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001043166 SCV001206885 pathogenic Hereditary breast ovarian cancer syndrome 2022-03-08 criteria provided, single submitter clinical testing Disruption of this splice site has been observed in individual(s) with breast and/or ovarian cancer (PMID: 29446198). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 13 of the BRCA1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. ClinVar contains an entry for this variant (Variation ID: 267547). For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in exon 13 skipping and introduces a premature termination codon (PMID: 21735045). The resulting mRNA is expected to undergo nonsense-mediated decay.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001043166 SCV001478721 pathogenic Hereditary breast ovarian cancer syndrome 2021-01-15 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.4484+1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. At least one publication reports experimental evidence confirming that this variant affects mRNA splicing (Menendez_2012). The variant was absent in 251172 control chromosomes (gnomAD). c.4484+1G>T has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer Syndrome (e.g. Judkins_2005, Sugano_2008, Menendez_2012, Shi_2017, Rebbeck_2018, Santonocito_2020). These data indicate that the variant is likely to be associated with disease. Three submitters have provided clinical-significance assessments for this variant in ClinVar after 2014, and all of them classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
CZECANCA consortium RCV001271024 SCV001451838 pathogenic Breast and/or ovarian cancer 2019-06-11 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.