rs707936

chr6-31765873-G-A

Variant summary

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

The NM_025258.3(VWA7):c.2499+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 1,612,670 control chromosomes in the GnomAD database, including 5,274 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 0.11 (1221 hom., cov: 32)
  • Exomes 𝑓: 0.068 (4053 hom.)
• Consequence: VWA7 NM_025258.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

Genes affected

VWA7 (HGNC:13939): (von Willebrand factor A domain containing 7) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWA7	NM_025258.3	c.2499+10C>T		intron_variant		ENST00000375688.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWA7	ENST00000375688.5	c.2499+10C>T		intron_variant		5	NM_025258.3	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16477 AN: 152148 Hom.: 1222 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0485

Gnomad AMR AF: 0.0700

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.0749

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0703

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0696

Gnomad OTH AF: 0.107

GnomAD3 exomes AF: 0.0802 AC: 19665 AN: 245104 Hom.: 1012 AF XY: 0.0800 AC XY: 10700 AN XY: 133684

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.0528

Gnomad ASJ exome AF: 0.0557

Gnomad EAS exome AF: 0.0930

Gnomad SAS exome AF: 0.0998

Gnomad FIN exome AF: 0.0701

Gnomad NFE exome AF: 0.0679

Gnomad OTH exome AF: 0.0735

GnomAD4 exome AF: 0.0677 AC: 98797 AN: 1460404 Hom.: 4053 Cov.: 34 AF XY: 0.0682 AC XY: 49556 AN XY: 726428

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.0562

Gnomad4 ASJ exome AF: 0.0546

Gnomad4 EAS exome AF: 0.0449

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0689

Gnomad4 NFE exome AF: 0.0616

Gnomad4 OTH exome AF: 0.0708

GnomAD4 genome AF: 0.108 AC: 16478 AN: 152266 Hom.: 1221 Cov.: 32 AF XY: 0.108 AC XY: 8018 AN XY: 74450

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.0697

Gnomad4 ASJ AF: 0.0524

Gnomad4 EAS AF: 0.0755

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0703

Gnomad4 NFE AF: 0.0696

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0765 Hom.: 747

Bravo AF: 0.113

Asia WGS AF: 0.0850 AC: 293 AN: 3478

EpiCase AF: 0.0694

EpiControl AF: 0.0713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.35
Dann	Benign	0.75

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: rs707936; hg19: chr6-31733650; COSMIC: COSV65173777; COSMIC: COSV65173777;