17-61777920-T-C

Position:

• chr17-61777920-T-C

Variant summary

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

The NM_032043.3(BRIP1):​c.1936-1358A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,108 control chromosomes in the GnomAD database, including 47,366 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 (47366 hom., cov: 30)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.1936-1358A>G		intron_variant		ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.1936-1358A>G		intron_variant		1	NM_032043.3	ENSP00000259008	P2

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119246 AN: 151990 Hom.: 47342 Cov.: 30

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.784 AC: 119315 AN: 152108 Hom.: 47366 Cov.: 30 AF XY: 0.785 AC XY: 58372 AN XY: 74382

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.768

Alfa AF: 0.750 Hom.: 43953

Bravo AF: 0.770

Asia WGS AF: 0.806 AC: 2802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9906313; hg19: chr17-59855281;