17-61685753-A-T

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.2905+83T>A variant causes a intron change. The variant allele was found at a frequency of 0.34 in 1,235,928 control chromosomes in the GnomAD database, including 73,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 8939 hom., cov: 32)

Exomes 𝑓: 0.34 ( 64644 hom. )

Consequence

BRIP1
NM_032043.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.84

Publications

10 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=-0.55).

BP6

Variant 17-61685753-A-T is Benign according to our data. Variant chr17-61685753-A-T is described in ClinVar as Benign. ClinVar VariationId is 1275841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3 link	c.2905+83T>A		intron_variant	Intron 19 of 19	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7 link	c.2905+83T>A		intron_variant	Intron 19 of 19	1	NM_032043.3	ENSP00000259008.2

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51474

AN:

151982

Hom.:

8931

Cov.:

show subpopulations

Gnomad AFR

AF:

0.353

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.357

GnomAD2 exomes

AF:

0.323

AC:

71041

AN:

219874

AF XY:

0.324

show subpopulations

Gnomad AFR exome

AF:

0.348

Gnomad AMR exome

AF:

0.226

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.499

Gnomad FIN exome

AF:

0.246

Gnomad NFE exome

AF:

0.348

Gnomad OTH exome

AF:

0.353

GnomAD4 exome

AF:

0.341

AC:

369281

AN:

1083828

Hom.:

64644

Cov.:

AF XY:

0.338

AC XY:

187764

AN XY:

555014

show subpopulations

African (AFR)

AF:

0.355

AC:

8965

AN:

25270

American (AMR)

AF:

0.229

AC:

9474

AN:

41440

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

7866

AN:

23394

East Asian (EAS)

AF:

0.468

AC:

17619

AN:

37682

South Asian (SAS)

AF:

0.265

AC:

20191

AN:

76198

European-Finnish (FIN)

AF:

0.255

AC:

11062

AN:

43380

Middle Eastern (MID)

AF:

0.404

AC:

1739

AN:

4302

European-Non Finnish (NFE)

AF:

0.351

AC:

275458

AN:

784194

Other (OTH)

AF:

0.352

AC:

16907

AN:

47968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

11760

23520

35280

47040

58800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7524

15048

22572

30096

37620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.339

AC:

51523

AN:

152100

Hom.:

8939

Cov.:

AF XY:

0.333

AC XY:

24773

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.353

AC:

14632

AN:

41482

American (AMR)

AF:

0.299

AC:

4571

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

1122

AN:

3468

East Asian (EAS)

AF:

0.490

AC:

2539

AN:

5178

South Asian (SAS)

AF:

0.263

AC:

1266

AN:

4820

European-Finnish (FIN)

AF:

0.243

AC:

2577

AN:

10600

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.348

AC:

23661

AN:

67950

Other (OTH)

AF:

0.360

AC:

761

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1746

3492

5238

6984

8730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.342

Hom.:

1682

Bravo

AF:

0.344

Asia WGS

AF:

0.334

AC:

1162

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

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

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.55

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

3.8

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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