rs6504063

Positions:

• chr17-61690140-G-A
• chr17-61690140-G-C

Variant summary

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

The NM_032043.3(BRIP1):​c.2575+3290C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,060 control chromosomes in the GnomAD database, including 28,849 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 0.61 (28849 hom., cov: 33)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

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 (AMR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRIP1	NM_032043.3	c.2575+3290C>T		intron_variant		ENST00000259008.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRIP1	ENST00000259008.7	c.2575+3290C>T		intron_variant		1	NM_032043.3	P2

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92550 AN: 151940 Hom.: 28811 Cov.: 33

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.609 AC: 92649 AN: 152060 Hom.: 28849 Cov.: 33 AF XY: 0.604 AC XY: 44883 AN XY: 74322

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.629

Alfa AF: 0.581 Hom.: 11955

Bravo AF: 0.640

Asia WGS AF: 0.532 AC: 1850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.76

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: rs6504063; hg19: chr17-59767501;