chr17-61686104-T-C

Variant names:

• chr17-61686104-T-C
• rs4986765
• NM_032043.3:c.2637A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032043.3(BRIP1):​c.2637A>G​(p.Glu879Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 1,613,482 control chromosomes in the GnomAD database, including 386,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (43212 hom., cov: 31)
  • Exomes 𝑓: 0.68 (343388 hom.)
• Consequence: BRIP1 NM_032043.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:20
• Conservation: PhyloP100: -0.191
• Publications: 54 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 17-61686104-T-C is Benign according to our data. Variant chr17-61686104-T-C is described in ClinVar as Benign. ClinVar VariationId is 183703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.191 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 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.2637A>G	p.Glu879Glu	synonymous	Exon 19 of 20	NP_114432.2	Q9BX63-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRIP1	ENST00000259008.7	TSL:1 MANE Select	c.2637A>G	p.Glu879Glu	synonymous	Exon 19 of 20	ENSP00000259008.2	Q9BX63-1
	BRIP1	ENST00000682453.1		c.2637A>G	p.Glu879Glu	synonymous	Exon 20 of 21	ENSP00000506943.1	Q9BX63-1
	BRIP1	ENST00000683039.1		c.2637A>G	p.Glu879Glu	synonymous	Exon 20 of 21	ENSP00000508303.1	Q9BX63-1

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112750 AN: 151928 Hom.: 43144 Cov.: 31

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.762

GnomAD2 exomes AF: 0.718 AC: 180347 AN: 251210 AF XY: 0.708

Gnomad AFR exome AF: 0.911

Gnomad AMR exome AF: 0.867

Gnomad ASJ exome AF: 0.696

Gnomad EAS exome AF: 0.891

Gnomad FIN exome AF: 0.509

Gnomad NFE exome AF: 0.663

Gnomad OTH exome AF: 0.727

GnomAD4 exome AF: 0.681 AC: 995610 AN: 1461436 Hom.: 343388 Cov.: 57 AF XY: 0.681 AC XY: 495081 AN XY: 727042

African (AFR) AF: 0.914 AC: 30602 AN: 33470

American (AMR) AF: 0.861 AC: 38516 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 18128 AN: 26132

East Asian (EAS) AF: 0.893 AC: 35421 AN: 39680

South Asian (SAS) AF: 0.702 AC: 60537 AN: 86248

European-Finnish (FIN) AF: 0.519 AC: 27701 AN: 53412

Middle Eastern (MID) AF: 0.783 AC: 4515 AN: 5768

European-Non Finnish (NFE) AF: 0.664 AC: 737810 AN: 1111620

Other (OTH) AF: 0.702 AC: 42380 AN: 60382

GnomAD4 genome AF: 0.742 AC: 112888 AN: 152046 Hom.: 43212 Cov.: 31 AF XY: 0.740 AC XY: 54992 AN XY: 74298

African (AFR) AF: 0.904 AC: 37523 AN: 41514

American (AMR) AF: 0.831 AC: 12698 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2436 AN: 3468

East Asian (EAS) AF: 0.893 AC: 4624 AN: 5178

South Asian (SAS) AF: 0.719 AC: 3462 AN: 4814

European-Finnish (FIN) AF: 0.496 AC: 5225 AN: 10540

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44606 AN: 67938

Other (OTH) AF: 0.764 AC: 1609 AN: 2106

Alfa AF: 0.701 Hom.: 115241

Bravo AF: 0.776

Asia WGS AF: 0.788 AC: 2743 AN: 3478

EpiCase AF: 0.678

EpiControl AF: 0.684

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	Hereditary cancer-predisposing syndrome (3)
-	-	3	not provided (3)
-	-	2	Familial cancer of breast (2)
-	-	2	Familial cancer of breast;C1836860:Fanconi anemia complementation group J (2)
-	-	2	Fanconi anemia complementation group J (2)
-	-	1	Hereditary breast ovarian cancer syndrome (1)
-	-	1	Ovarian cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.2
DANN	Benign	0.62
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4986765; hg19: chr17-59763465; COSMIC: COSV108056376;