rs9908659

chr17-61847501-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032043.3(BRIP1):c.508-281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,992 control chromosomes in the GnomAD database, including 12,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (12426 hom., cov: 32)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.52

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-61847501-T-C is Benign according to our data. Variant chr17-61847501-T-C is described in ClinVar as [Benign]. Clinvar id is 1236703.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRIP1	NM_032043.3	c.508-281A>G		intron_variant		ENST00000259008.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRIP1	ENST00000259008.7	c.508-281A>G		intron_variant		1	NM_032043.3	P2

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59977 AN: 151874 Hom.: 12418 Cov.: 32

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.395 AC: 60015 AN: 151992 Hom.: 12426 Cov.: 32 AF XY: 0.389 AC XY: 28886 AN XY: 74286

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.340

Alfa AF: 0.403 Hom.: 2545

Bravo AF: 0.387

Asia WGS AF: 0.221 AC: 762 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.10
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs9908659; hg19: chr17-59924862;