rs60657820

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.*2090G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 199,364 control chromosomes in the GnomAD database, including 14,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11484 hom., cov: 31)

Exomes 𝑓: 0.35 ( 2976 hom. )

Consequence

BRIP1
NM_032043.3 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.505

Publications

3 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=-1.02).

BP6

Variant 17-61681206-C-G is Benign according to our data. Variant chr17-61681206-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3 link	c.*2090G>C		3_prime_UTR_variant	Exon 20 of 20	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.*2090G>C		3_prime_UTR_variant	Exon 20 of 20	1	NM_032043.3	ENSP00000259008.2		Q9BX63-1

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57556

AN:

151414

Hom.:

11465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.274

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.485

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.378

GnomAD4 exome

AF:

0.347

AC:

16615

AN:

47830

Hom.:

2976

AF XY:

0.346

AC XY:

7671

AN XY:

22152

show subpopulations

African (AFR)

AF:

0.477

AC:

933

AN:

1958

American (AMR)

AF:

0.257

AC:

367

AN:

1430

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

955

AN:

3198

East Asian (EAS)

AF:

0.427

AC:

3222

AN:

7554

South Asian (SAS)

AF:

0.232

AC:

AN:

396

European-Finnish (FIN)

AF:

0.206

AC:

AN:

Middle Eastern (MID)

AF:

0.366

AC:

104

AN:

284

European-Non Finnish (NFE)

AF:

0.331

AC:

9611

AN:

29022

Other (OTH)

AF:

0.335

AC:

1324

AN:

3954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

455

910

1365

1820

2275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.380

AC:

57628

AN:

151534

Hom.:

11484

Cov.:

AF XY:

0.373

AC XY:

27611

AN XY:

74068

show subpopulations

African (AFR)

AF:

0.505

AC:

20832

AN:

41268

American (AMR)

AF:

0.315

AC:

4800

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.305

AC:

1056

AN:

3466

East Asian (EAS)

AF:

0.485

AC:

2473

AN:

5094

South Asian (SAS)

AF:

0.263

AC:

1267

AN:

4818

European-Finnish (FIN)

AF:

0.242

AC:

2559

AN:

10558

Middle Eastern (MID)

AF:

0.469

AC:

135

AN:

288

European-Non Finnish (NFE)

AF:

0.346

AC:

23457

AN:

67796

Other (OTH)

AF:

0.381

AC:

801

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1723

3446

5169

6892

8615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.217

Hom.:

442

Bravo

AF:

0.394

Asia WGS

AF:

0.343

AC:

1191

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 29, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia complementation group J

Benign:1

Jan 12, 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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.8

(source)

DANN

Benign

0.39

PhyloP100

-0.51

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over