Genetic Variant BRIP1:c.*2815_*2816insAGAAA (chr17-61680480-C-CTTTCT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_032043.3(BRIP1):c.*2815_*2816insAGAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0052 ( 23 hom., cov: 0)

Consequence

BRIP1
NM_032043.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.0550

Publications

0 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 -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00517 (642/124070) while in subpopulation AFR AF = 0.0168 (532/31740). AF 95% confidence interval is 0.0156. There are 23 homozygotes in GnomAd4. There are 315 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 23 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3 link	c.2815_2816insAGAAA		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.2815_2816insAGAAA		3_prime_UTR_variant	Exon 20 of 20	1	NM_032043.3	ENSP00000259008.2		Q9BX63-1
BRIP1	ENST00000682755.1 link	c.2815_2816insAGAAA		3_prime_UTR_variant	Exon 18 of 18			ENSP00000507660.1		A0A804HJV4

Frequencies

GnomAD3 genomes

AF:

0.00515

AC:

639

AN:

124094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00580

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000482

Gnomad SAS

AF:

0.000504

Gnomad FIN

AF:

0.000935

Gnomad MID

AF:

0.00962

Gnomad NFE

AF:

0.000357

Gnomad OTH

AF:

0.00676

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.00517

AC:

642

AN:

124070

Hom.:

Cov.:

AF XY:

0.00538

AC XY:

315

AN XY:

58552

show subpopulations

African (AFR)

AF:

0.0168

AC:

532

AN:

31740

American (AMR)

AF:

0.00580

AC:

AN:

11378

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3230

East Asian (EAS)

AF:

0.000484

AC:

AN:

4134

South Asian (SAS)

AF:

0.000507

AC:

AN:

3944

European-Finnish (FIN)

AF:

0.000935

AC:

AN:

5350

Middle Eastern (MID)

AF:

0.0100

AC:

AN:

200

European-Non Finnish (NFE)

AF:

0.000357

AC:

AN:

61624

Other (OTH)

AF:

0.00677

AC:

AN:

1626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Fanconi anemia

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breast neoplasm

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.055

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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17-61680480-C-CTTTCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over