17-61863458-C-T

Variant names:

• chr17-61863458-C-T
• rs2048718
• NM_032043.3:c.-205G>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.-205G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,882 control chromosomes in the GnomAD database, including 15,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15228 hom., cov: 29)
  • Exomes 𝑓: 0.47 (24 hom.)
• Consequence: BRIP1 NM_032043.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.615
• Publications: 38 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=-0.78).
• BP6: Variant 17-61863458-C-T is Benign according to our data. Variant chr17-61863458-C-T is described in ClinVar as Benign. ClinVar VariationId is 324354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 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.-205G>A		5_prime_UTR	Exon 1 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.-205G>A		5_prime_UTR	Exon 1 of 20	ENSP00000259008.2	Q9BX63-1
	BRIP1	ENST00000854939.1		c.-201G>A		5_prime_UTR	Exon 1 of 20	ENSP00000524998.1
	BRIP1	ENST00000923498.1		c.-205G>A		5_prime_UTR	Exon 1 of 20	ENSP00000593557.1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64667 AN: 151538 Hom.: 15209 Cov.: 29

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.469 AC: 106 AN: 226 Hom.: 24 Cov.: 0 AF XY: 0.488 AC XY: 83 AN XY: 170

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 2 AN: 6

East Asian (EAS) AF: 0.750 AC: 6 AN: 8

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.446 AC: 83 AN: 186

Other (OTH) AF: 0.700 AC: 7 AN: 10

GnomAD4 genome AF: 0.427 AC: 64724 AN: 151656 Hom.: 15228 Cov.: 29 AF XY: 0.439 AC XY: 32548 AN XY: 74086

African (AFR) AF: 0.246 AC: 10177 AN: 41352

American (AMR) AF: 0.530 AC: 8090 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1544 AN: 3466

East Asian (EAS) AF: 0.798 AC: 4096 AN: 5132

South Asian (SAS) AF: 0.671 AC: 3209 AN: 4780

European-Finnish (FIN) AF: 0.530 AC: 5567 AN: 10512

Middle Eastern (MID) AF: 0.438 AC: 127 AN: 290

European-Non Finnish (NFE) AF: 0.449 AC: 30438 AN: 67858

Other (OTH) AF: 0.452 AC: 952 AN: 2106

Alfa AF: 0.440 Hom.: 45581

Bravo AF: 0.419

Asia WGS AF: 0.680 AC: 2364 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Fanconi anemia complementation group J (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.5
DANN	Benign	0.62
PhyloP100		-0.61
PromoterAI		-0.018	Neutral
Mutation Taster		=300/0	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: rs2048718; hg19: chr17-59940819;