12-6055289-C-T

Variant summary

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

The NM_000552.5(VWF):c.1945+1568G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,112 control chromosomes in the GnomAD database, including 13,246 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 0.40 (13246 hom., cov: 32)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.48

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWF	NM_000552.5	c.1945+1568G>A		intron_variant		ENST00000261405.10
VWF	XM_047429501.1	c.1945+1568G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWF	ENST00000261405.10	c.1945+1568G>A		intron_variant		1	NM_000552.5	P1
VWF	ENST00000538635.5	n.420+55226G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60732 AN: 151994 Hom.: 13221 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.400 AC: 60799 AN: 152112 Hom.: 13246 Cov.: 32 AF XY: 0.392 AC XY: 29139 AN XY: 74360

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.387

Alfa AF: 0.389 Hom.: 2136

Bravo AF: 0.401

Asia WGS AF: 0.274 AC: 957 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	0.0050
Dann	Benign	0.73

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: rs12304995; hg19: chr12-6164455;