rs4764478

Positions:

• chr12-5968959-T-A

Variant summary

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

The NM_000552.5(VWF):​c.7729+252A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,098 control chromosomes in the GnomAD database, including 3,652 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 0.21 (3652 hom., cov: 33)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

Genes affected

VWF (HGNC:12726): (von Willebrand factor) This gene encodes a glycoprotein involved in hemostasis. The encoded preproprotein is proteolytically processed following assembly into large multimeric complexes. These complexes function in the adhesion of platelets to sites of vascular injury and the transport of various proteins in the blood. Mutations in this gene result in von Willebrand disease, an inherited bleeding disorder. An unprocessed pseudogene has been found on chromosome 22. [provided by RefSeq, Oct 2015]

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 = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWF	NM_000552.5	c.7729+252A>T		intron_variant		ENST00000261405.10
VWF	XM_047429501.1	c.7729+252A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWF	ENST00000261405.10	c.7729+252A>T		intron_variant		1	NM_000552.5	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32560 AN: 151980 Hom.: 3648 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.0658

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.214 AC: 32584 AN: 152098 Hom.: 3652 Cov.: 33 AF XY: 0.210 AC XY: 15582 AN XY: 74360

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.0661

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.215

Alfa AF: 0.214 Hom.: 484

Bravo AF: 0.215

Asia WGS AF: 0.175 AC: 613 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	0.31
DANN	Benign	0.81

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: rs4764478; hg19: chr12-6078125;