NM_032043.3:c.1340+109G>A

Variant names:

• chr17-61798991-C-T
• rs2191248
• NM_032043.3:c.1340+109G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032043.3(BRIP1):​c.1340+109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,019,488 control chromosomes in the GnomAD database, including 54,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6259 hom., cov: 32)
  • Exomes 𝑓: 0.32 (47826 hom.)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.51
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 17-61798991-C-T is Benign according to our data. Variant chr17-61798991-C-T is described in ClinVar as Benign. ClinVar VariationId is 1263501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 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.1340+109G>A		intron	N/A	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.1340+109G>A		intron	N/A	ENSP00000259008.2	Q9BX63-1
	BRIP1	ENST00000682453.1		c.1340+109G>A		intron	N/A	ENSP00000506943.1	Q9BX63-1
	BRIP1	ENST00000683039.1		c.1340+109G>A		intron	N/A	ENSP00000508303.1	Q9BX63-1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39216 AN: 151794 Hom.: 6266 Cov.: 32

Gnomad AFR AF: 0.0807

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.323 AC: 279961 AN: 867576 Hom.: 47826 AF XY: 0.321 AC XY: 145689 AN XY: 453240

African (AFR) AF: 0.0725 AC: 1561 AN: 21540

American (AMR) AF: 0.213 AC: 8374 AN: 39386

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 6077 AN: 22126

East Asian (EAS) AF: 0.151 AC: 5408 AN: 35872

South Asian (SAS) AF: 0.251 AC: 17872 AN: 71218

European-Finnish (FIN) AF: 0.394 AC: 16592 AN: 42142

Middle Eastern (MID) AF: 0.205 AC: 755 AN: 3674

European-Non Finnish (NFE) AF: 0.358 AC: 211257 AN: 590832

Other (OTH) AF: 0.296 AC: 12065 AN: 40786

GnomAD4 genome AF: 0.258 AC: 39202 AN: 151912 Hom.: 6259 Cov.: 32 AF XY: 0.256 AC XY: 19016 AN XY: 74228

African (AFR) AF: 0.0805 AC: 3342 AN: 41502

American (AMR) AF: 0.246 AC: 3747 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 931 AN: 3462

East Asian (EAS) AF: 0.128 AC: 661 AN: 5166

South Asian (SAS) AF: 0.236 AC: 1138 AN: 4822

European-Finnish (FIN) AF: 0.387 AC: 4070 AN: 10526

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.359 AC: 24380 AN: 67906

Other (OTH) AF: 0.240 AC: 506 AN: 2108

Alfa AF: 0.266 Hom.: 5382

Bravo AF: 0.237

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary breast ovarian cancer syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	16
DANN	Benign	0.60
PhyloP100		1.5
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: rs2191248; hg19: chr17-59876352; COSMIC: COSV51993315;