NM_032043.3:c.628-13672C>A

Variant names:

• chr17-61822429-G-T
• rs6504074
• NM_032043.3:c.628-13672C>A

Variant summary

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

The NM_032043.3(BRIP1):​c.628-13672C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 151,932 control chromosomes in the GnomAD database, including 10,702 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 0.35 (10702 hom., cov: 31)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

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 (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.628-13672C>A		intron_variant	Intron 6 of 19	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.628-13672C>A		intron_variant	Intron 6 of 19	1	NM_032043.3	ENSP00000259008.2

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53773 AN: 151814 Hom.: 10679 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.354 AC: 53849 AN: 151932 Hom.: 10702 Cov.: 31 AF XY: 0.358 AC XY: 26552 AN XY: 74244

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.336

Alfa AF: 0.265 Hom.: 2633

Bravo AF: 0.369

Asia WGS AF: 0.361 AC: 1255 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	1.6
DANN	Benign	0.41

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: rs6504074; hg19: chr17-59899790;