Submissions for variant NM_032043.3(BRIP1):c.3099T>C (p.Pro1033=)

gnomAD frequency: 0.00013  dbSNP: rs202228407

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163110	SCV000213620	likely benign	Hereditary cancer-predisposing syndrome	2014-06-26	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086591	SCV000252877	benign	Familial cancer of breast; Fanconi anemia complementation group J	2025-02-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000409374	SCV000404578	likely benign	Fanconi anemia complementation group J	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Counsyl	RCV000409374	SCV000490041	likely benign	Fanconi anemia complementation group J	2016-10-11	criteria provided, single submitter	clinical testing
Counsyl	RCV000410011	SCV000490042	likely benign	Ovarian neoplasm	2016-10-11	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163110	SCV000684247	benign	Hereditary cancer-predisposing syndrome	2016-11-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588516	SCV000699712	benign	not provided	2016-05-09	criteria provided, single submitter	clinical testing	Variant summary: The BRIP1 c.3099T>C (p.Pro1033Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 75/121402 control chromosomes (2 homozygotes), predominantly observed in the Latino subpopulation at a frequency of 0.0064778 (75/11578). This frequency is about 104 times the estimated maximal expected allele frequency of a pathogenic BRIP1 variant (0.0000625), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
PreventionGenetics, part of Exact Sciences	RCV000506953	SCV000807142	benign	not specified	2017-03-07	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588516	SCV000883523	likely benign	not provided	2024-02-29	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000588516	SCV000887998	benign	not provided	2022-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000588516	SCV001756754	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000506953	SCV002067648	benign	not specified	2018-11-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163110	SCV002533675	benign	Hereditary cancer-predisposing syndrome	2021-09-15	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV001086591	SCV002794660	likely benign	Familial cancer of breast; Fanconi anemia complementation group J	2021-10-11	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003315986	SCV004019344	benign	Familial cancer of breast	2023-02-28	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.