rs2239138

Positions:

• chr12-5973392-A-T

Variant summary

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

The NM_000552.5(VWF):​c.7438-1683T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,126 control chromosomes in the GnomAD database, including 34,525 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 0.67 (34525 hom., cov: 33)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWF	NM_000552.5	c.7438-1683T>A		intron_variant		ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.7438-1683T>A		intron_variant			XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.7438-1683T>A		intron_variant		1	NM_000552.5	ENSP00000261405	P1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101295 AN: 152008 Hom.: 34498 Cov.: 33

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.666 AC: 101367 AN: 152126 Hom.: 34525 Cov.: 33 AF XY: 0.661 AC XY: 49165 AN XY: 74356

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.693

Alfa AF: 0.664 Hom.: 4201

Bravo AF: 0.668

Asia WGS AF: 0.450 AC: 1572 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	8.7
DANN	Benign	0.53

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: rs2239138; hg19: chr12-6082558;