rs8076727

Positions:

• chr17-61837320-G-A

Variant summary

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

The NM_032043.3(BRIP1):​c.627+9781C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 151,896 control chromosomes in the GnomAD database, including 3,312 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 0.19 (3312 hom., cov: 31)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.627+9781C>T		intron_variant		ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.627+9781C>T		intron_variant		1	NM_032043.3	ENSP00000259008	P2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29400 AN: 151778 Hom.: 3305 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0290

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.194 AC: 29419 AN: 151896 Hom.: 3312 Cov.: 31 AF XY: 0.194 AC XY: 14398 AN XY: 74230

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.0287

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.212

Alfa AF: 0.217 Hom.: 677

Bravo AF: 0.200

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.21
DANN	Benign	0.58

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: rs8076727; hg19: chr17-59914681;