chr17-61749264-G-T

Variant names:

• chr17-61749264-G-T
• rs2159450
• NM_032043.3:c.2098-4673C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032043.3(BRIP1):​c.2098-4673C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 151,948 control chromosomes in the GnomAD database, including 46,646 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (46646 hom., cov: 30)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.2098-4673C>A		intron_variant	Intron 14 of 19	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.2098-4673C>A		intron_variant	Intron 14 of 19	1	NM_032043.3	ENSP00000259008.2

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118294 AN: 151830 Hom.: 46623 Cov.: 30

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.822

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.779 AC: 118363 AN: 151948 Hom.: 46646 Cov.: 30 AF XY: 0.779 AC XY: 57856 AN XY: 74262

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.764

Alfa AF: 0.735 Hom.: 3387

Bravo AF: 0.763

Asia WGS AF: 0.800 AC: 2780 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.75
DANN	Benign	0.73

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: rs2159450; hg19: chr17-59826625;