chr17-61862883-A-G

Position:

• chr17-61862883-A-G

Variant summary

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

The NM_032043.3(BRIP1):​c.-31+401T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,106 control chromosomes in the GnomAD database, including 2,711 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 0.18 (2711 hom., cov: 31)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRIP1	NM_032043.3	c.-31+401T>C		intron_variant		ENST00000259008.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRIP1	ENST00000259008.7	c.-31+401T>C		intron_variant		1	NM_032043.3	P2

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26653 AN: 151988 Hom.: 2703 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.175 AC: 26680 AN: 152106 Hom.: 2711 Cov.: 31 AF XY: 0.181 AC XY: 13485 AN XY: 74366

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.181

Alfa AF: 0.165 Hom.: 457

Bravo AF: 0.171

Asia WGS AF: 0.321 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs16945692; hg19: chr17-59940244;