NM_032043.3:c.2905+83T>A

Variant names:

• chr17-61685753-A-T
• rs4988357
• NM_032043.3:c.2905+83T>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.2905+83T>A variant causes a intron change. The variant allele was found at a frequency of 0.34 in 1,235,928 control chromosomes in the GnomAD database, including 73,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (8939 hom., cov: 32)
  • Exomes 𝑓: 0.34 (64644 hom.)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 3.84
• Publications: 10 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: Orphanet, Illumina
• Fanconi anemia complementation group J

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: ClinGen, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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=-0.55).
• BP6: Variant 17-61685753-A-T is Benign according to our data. Variant chr17-61685753-A-T is described in ClinVar as Benign. ClinVar VariationId is 1275841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 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.2905+83T>A		intron	N/A	NP_114432.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRIP1	ENST00000259008.7	TSL:1 MANE Select	c.2905+83T>A		intron	N/A	ENSP00000259008.2
	BRIP1	ENST00000577598.5	TSL:5	c.*3T>A		3_prime_UTR	Exon 18 of 18	ENSP00000464654.1
	BRIP1	ENST00000682453.1		c.2905+83T>A		intron	N/A	ENSP00000506943.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51474 AN: 151982 Hom.: 8931 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.357

GnomAD2 exomes AF: 0.323 AC: 71041 AN: 219874 AF XY: 0.324

Gnomad AFR exome AF: 0.348

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.332

Gnomad EAS exome AF: 0.499

Gnomad FIN exome AF: 0.246

Gnomad NFE exome AF: 0.348

Gnomad OTH exome AF: 0.353

GnomAD4 exome AF: 0.341 AC: 369281 AN: 1083828 Hom.: 64644 Cov.: 15 AF XY: 0.338 AC XY: 187764 AN XY: 555014

African (AFR) AF: 0.355 AC: 8965 AN: 25270

American (AMR) AF: 0.229 AC: 9474 AN: 41440

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 7866 AN: 23394

East Asian (EAS) AF: 0.468 AC: 17619 AN: 37682

South Asian (SAS) AF: 0.265 AC: 20191 AN: 76198

European-Finnish (FIN) AF: 0.255 AC: 11062 AN: 43380

Middle Eastern (MID) AF: 0.404 AC: 1739 AN: 4302

European-Non Finnish (NFE) AF: 0.351 AC: 275458 AN: 784194

Other (OTH) AF: 0.352 AC: 16907 AN: 47968

GnomAD4 genome AF: 0.339 AC: 51523 AN: 152100 Hom.: 8939 Cov.: 32 AF XY: 0.333 AC XY: 24773 AN XY: 74392

African (AFR) AF: 0.353 AC: 14632 AN: 41482

American (AMR) AF: 0.299 AC: 4571 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1122 AN: 3468

East Asian (EAS) AF: 0.490 AC: 2539 AN: 5178

South Asian (SAS) AF: 0.263 AC: 1266 AN: 4820

European-Finnish (FIN) AF: 0.243 AC: 2577 AN: 10600

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23661 AN: 67950

Other (OTH) AF: 0.360 AC: 761 AN: 2112

Alfa AF: 0.342 Hom.: 1682

Bravo AF: 0.344

Asia WGS AF: 0.334 AC: 1162 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Hereditary breast ovarian cancer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Benign	0.89
PhyloP100		3.8
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: rs4988357; hg19: chr17-59763114; COSMIC: COSV51997887;