17-61683635-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032043.3(BRIP1):c.3411T>C(p.Tyr1137Tyr) 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:20

Conservation

PhyloP100: 3.27

Publications

44 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: Illumina, Orphanet
Fanconi anemia complementation group J
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
hereditary breast carcinoma
Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, ClinGen
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 -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 VariationId is 183702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032043.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRIP1	NM_032043.3	MANE Select	c.3411T>C	p.Tyr1137Tyr	synonymous	Exon 20 of 20	NP_114432.2	Q9BX63-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRIP1	ENST00000259008.7	TSL:1 MANE Select	c.3411T>C	p.Tyr1137Tyr	synonymous	Exon 20 of 20	ENSP00000259008.2	Q9BX63-1
BRIP1	ENST00000682453.1		c.3411T>C	p.Tyr1137Tyr	synonymous	Exon 21 of 21	ENSP00000506943.1	Q9BX63-1
BRIP1	ENST00000683039.1		c.3411T>C	p.Tyr1137Tyr	synonymous	Exon 21 of 21	ENSP00000508303.1	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

GnomAD2 exomes

AF:

0.599

AC:

149716

AN:

249818

AF XY:

0.586

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 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

African (AFR)

AF:

0.651

AC:

21796

AN:

33480

American (AMR)

AF:

0.785

AC:

35088

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

14923

AN:

26134

East Asian (EAS)

AF:

0.741

AC:

29416

AN:

39682

South Asian (SAS)

AF:

0.459

AC:

39596

AN:

86244

European-Finnish (FIN)

AF:

0.431

AC:

22329

AN:

51858

Middle Eastern (MID)

AF:

0.654

AC:

3770

AN:

5766

European-Non Finnish (NFE)

AF:

0.595

AC:

661223

AN:

1111796

Other (OTH)

AF:

0.592

AC:

35743

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

21212

42423

63635

84846

106058

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18214

36428

54642

72856

91070

<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:

0.605

AC:

91973

AN:

152020

Hom.:

28414

Cov.:

AF XY:

0.600

AC XY:

44569

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.651

AC:

27002

AN:

41450

American (AMR)

AF:

0.734

AC:

11220

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.586

AC:

2035

AN:

3472

East Asian (EAS)

AF:

0.721

AC:

3730

AN:

5172

South Asian (SAS)

AF:

0.459

AC:

2217

AN:

4828

European-Finnish (FIN)

AF:

0.408

AC:

4302

AN:

10552

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.583

AC:

39615

AN:

67948

Other (OTH)

AF:

0.626

AC:

1321

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1844

3689

5533

7378

9222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.600

Hom.:

111791

Bravo

AF:

0.635

Asia WGS

AF:

0.533

AC:

1854

AN:

3478

EpiCase

AF:

0.595

EpiControl

AF:

0.609

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Hereditary cancer-predisposing syndrome (3)

not provided (3)

Familial cancer of breast (2)

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

Fanconi anemia complementation group J (2)

Hereditary breast ovarian cancer syndrome (1)

Ovarian cancer (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.1

(source)

DANN

Benign

0.53

PhyloP100

3.3

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over