Variant rs4986763 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032043.3(BRIP1):c.3411T>C(p.Tyr1137=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,612,072 control chromosomes in the GnomAD database, including 287,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 28414 hom., cov: 31)

Exomes 𝑓: 0.59 ( 258912 hom. )

Consequence

BRIP1
NM_032043.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:18

Conservation

PhyloP100: 3.27

Variant links:

Genes affected

BRIP1 (HGNC:20473): (BRCA1 interacting helicase 1) The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations. [provided by RefSeq, Jul 2008]

BRIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 17-61683635-A-G is Benign according to our data. Variant chr17-61683635-A-G is described in ClinVar as [Benign]. Clinvar id is 183702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-61683635-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=3.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRIP1	NM_032043.3 linkuse as main transcript	c.3411T>C	p.Tyr1137=	synonymous_variant	20/20	ENST00000259008.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRIP1	ENST00000259008.7 linkuse as main transcript	c.3411T>C	p.Tyr1137=	synonymous_variant	20/20	1	NM_032043.3	P2	Q9BX63-1

Frequencies

GnomAD3 genomes

AF:

0.605

AC:

91875

AN:

151900

Hom.:

28379

Cov.:

show subpopulations

Gnomad AFR

AF:

0.652

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.734

Gnomad ASJ

AF:

0.586

Gnomad EAS

AF:

0.720

Gnomad SAS

AF:

0.458

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.626

GnomAD3 exomes

AF:

0.599

AC:

149716

AN:

249818

Hom.:

46517

AF XY:

0.586

AC XY:

79261

AN XY:

135268

show subpopulations

Gnomad AFR exome

AF:

0.654

Gnomad AMR exome

AF:

0.794

Gnomad ASJ exome

AF:

0.571

Gnomad EAS exome

AF:

0.715

Gnomad SAS exome

AF:

0.455

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.587

Gnomad OTH exome

AF:

0.619

GnomAD4 exome

AF:

0.592

AC:

863884

AN:

1460052

Hom.:

258912

Cov.:

AF XY:

0.587

AC XY:

426155

AN XY:

726384

show subpopulations

Gnomad4 AFR exome

AF:

0.651

Gnomad4 AMR exome

AF:

0.785

Gnomad4 ASJ exome

AF:

0.571

Gnomad4 EAS exome

AF:

0.741

Gnomad4 SAS exome

AF:

0.459

Gnomad4 FIN exome

AF:

0.431

Gnomad4 NFE exome

AF:

0.595

Gnomad4 OTH exome

AF:

0.592

GnomAD4 genome

AF:

0.605

AC:

91973

AN:

152020

Hom.:

28414

Cov.:

AF XY:

0.600

AC XY:

44569

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.651

Gnomad4 AMR

AF:

0.734

Gnomad4 ASJ

AF:

0.586

Gnomad4 EAS

AF:

0.721

Gnomad4 SAS

AF:

0.459

Gnomad4 FIN

AF:

0.408

Gnomad4 NFE

AF:

0.583

Gnomad4 OTH

AF:

0.626

Alfa

AF:

0.599

Hom.:

51434

Bravo

AF:

0.635

Asia WGS

AF:

0.533

AC:

1854

AN:

3478

EpiCase

AF:

0.595

EpiControl

AF:

0.609

ClinVar

Significance: Benign

Submissions summary: Benign:18

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	curation	Leiden Open Variation Database	Aug 13, 2019	Curator: Arleen D. Auerbach. Submitters to LOVD: Maximiliano Zeballos, Yukihide Momozawa. -

Familial cancer of breast;C1836860:Fanconi anemia complementation group J

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Mar 23, 2022	- -

Fanconi anemia complementation group J

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Counsyl	Jun 18, 2016	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Hereditary cancer-predisposing syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Nov 11, 2014	This alteration is classified as 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. -
Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Mar 31, 2015	- -

Familial cancer of breast

Benign:2

Benign, criteria provided, single submitter	clinical testing	Myriad Genetics, Inc.	Feb 28, 2023	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

Hereditary breast ovarian cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Ovarian neoplasm

Benign:1

Benign, criteria provided, single submitter

clinical testing

Counsyl

Jun 18, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.1

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over