17-61847251-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032043.3(BRIP1):c.508-31C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,610,738 control chromosomes in the GnomAD database, including 27,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2453 hom., cov: 32)

Exomes 𝑓: 0.17 ( 24923 hom. )

Consequence

BRIP1
NM_032043.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.19

Publications

24 publications found

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 Gene-Disease associations (from GenCC):

familial ovarian cancer
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Fanconi anemia
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina
Fanconi anemia complementation group J
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
hereditary breast carcinoma
Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
colorectal adenoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

BRIP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-61847251-G-C is Benign according to our data. Variant chr17-61847251-G-C is described in ClinVar as [Benign]. Clinvar id is 262007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3 link	c.508-31C>G		intron_variant	Intron 5 of 19	ENST00000259008.7	NP_114432.2	Q9BX63-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7 link	c.508-31C>G		intron_variant	Intron 5 of 19	1	NM_032043.3	ENSP00000259008.2		Q9BX63-1

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24067

AN:

152014

Hom.:

2448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0749

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.540

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.161

GnomAD2 exomes

AF:

0.197

AC:

49391

AN:

250934

AF XY:

0.194

show subpopulations

Gnomad AFR exome

AF:

0.0715

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.165

Gnomad EAS exome

AF:

0.556

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.186

GnomAD4 exome

AF:

0.172

AC:

250151

AN:

1458606

Hom.:

24923

Cov.:

AF XY:

0.171

AC XY:

123952

AN XY:

725860

show subpopulations

African (AFR)

AF:

0.0699

AC:

2336

AN:

33440

American (AMR)

AF:

0.187

AC:

8356

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

4355

AN:

26100

East Asian (EAS)

AF:

0.525

AC:

20784

AN:

39578

South Asian (SAS)

AF:

0.157

AC:

13562

AN:

86172

European-Finnish (FIN)

AF:

0.263

AC:

13969

AN:

53124

Middle Eastern (MID)

AF:

0.137

AC:

788

AN:

5758

European-Non Finnish (NFE)

AF:

0.158

AC:

175258

AN:

1109420

Other (OTH)

AF:

0.178

AC:

10743

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

9171

18342

27514

36685

45856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.158

AC:

24088

AN:

152132

Hom.:

2453

Cov.:

AF XY:

0.165

AC XY:

12281

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0751

AC:

3118

AN:

41544

American (AMR)

AF:

0.167

AC:

2548

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

568

AN:

3468

East Asian (EAS)

AF:

0.540

AC:

2797

AN:

5178

South Asian (SAS)

AF:

0.165

AC:

798

AN:

4822

European-Finnish (FIN)

AF:

0.272

AC:

2862

AN:

10540

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10956

AN:

67984

Other (OTH)

AF:

0.167

AC:

352

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

996

1992

2987

3983

4979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.153

Hom.:

375

Bravo

AF:

0.151

Asia WGS

AF:

0.312

AC:

1084

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

- -

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance:Benign

Review Status:no assertion criteria provided

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:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial cancer of breast

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.11

(source)

DANN

Benign

0.62

PhyloP100

-2.2

PromoterAI

0.052

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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17-61847251-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over