17-61686104-T-C

Variant names:

• chr17-61686104-T-C
• rs4986765
• NM_032043.3:c.2637A>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032043.3(BRIP1):​c.2637A>G​(p.Glu879Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 1,613,482 control chromosomes in the GnomAD database, including 386,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (43212 hom., cov: 31)
  • Exomes 𝑓: 0.68 (343388 hom.)
• Consequence: BRIP1 NM_032043.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:19
• Conservation: PhyloP100: -0.191

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 17-61686104-T-C is Benign according to our data. Variant chr17-61686104-T-C is described in ClinVar as [Benign]. Clinvar id is 183703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-61686104-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.191 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.2637A>G	p.Glu879Glu	synonymous_variant	Exon 19 of 20	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.2637A>G	p.Glu879Glu	synonymous_variant	Exon 19 of 20	1	NM_032043.3	ENSP00000259008.2

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112750 AN: 151928 Hom.: 43144 Cov.: 31

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.762

GnomAD3 exomes AF: 0.718 AC: 180347 AN: 251210 Hom.: 66500 AF XY: 0.708 AC XY: 96185 AN XY: 135814

Gnomad AFR exome AF: 0.911

Gnomad AMR exome AF: 0.867

Gnomad ASJ exome AF: 0.696

Gnomad EAS exome AF: 0.891

Gnomad SAS exome AF: 0.699

Gnomad FIN exome AF: 0.509

Gnomad NFE exome AF: 0.663

Gnomad OTH exome AF: 0.727

GnomAD4 exome AF: 0.681 AC: 995610 AN: 1461436 Hom.: 343388 Cov.: 57 AF XY: 0.681 AC XY: 495081 AN XY: 727042

Gnomad4 AFR exome AF: 0.914

Gnomad4 AMR exome AF: 0.861

Gnomad4 ASJ exome AF: 0.694

Gnomad4 EAS exome AF: 0.893

Gnomad4 SAS exome AF: 0.702

Gnomad4 FIN exome AF: 0.519

Gnomad4 NFE exome AF: 0.664

Gnomad4 OTH exome AF: 0.702

GnomAD4 genome AF: 0.742 AC: 112888 AN: 152046 Hom.: 43212 Cov.: 31 AF XY: 0.740 AC XY: 54992 AN XY: 74298

Gnomad4 AFR AF: 0.904

Gnomad4 AMR AF: 0.831

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.893

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.764

Alfa AF: 0.692 Hom.: 45456

Bravo AF: 0.776

Asia WGS AF: 0.788 AC: 2743 AN: 3478

EpiCase AF: 0.678

EpiControl AF: 0.684

ClinVar

Significance: Benign

Submissions summary: Benign:19

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Aug 13, 2019

Leiden Open Variation Database

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: curation

Curator: Arleen D. Auerbach. Submitters to LOVD: Maximiliano Zeballos, Yukihide Momozawa. -

-

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial cancer of breast;C1836860:Fanconi anemia complementation group J Benign:2

Mar 23, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fanconi anemia complementation group J Benign:2

Jun 18, 2016

Counsyl

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Familial cancer of breast Benign:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 28, 2023

Myriad Genetics, Inc.

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

Hereditary cancer-predisposing syndrome Benign:2

Nov 07, 2014

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Mar 31, 2015

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary breast ovarian cancer syndrome Benign:1

Apr 19, 2022

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ovarian neoplasm Benign:1

Jun 18, 2016

Counsyl

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.2
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs4986765; hg19: chr17-59763465;