rs2270152

chr12-5951903-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000552.5(VWF):c.8116-20A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,612,966 control chromosomes in the GnomAD database, including 35,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2428 hom., cov: 32)
  • Exomes 𝑓: 0.21 (32613 hom.)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.45

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-5951903-T-G is Benign according to our data. Variant chr12-5951903-T-G is described in ClinVar as [Benign]. Clinvar id is 256703.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-5951903-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWF	NM_000552.5	c.8116-20A>C		intron_variant		ENST00000261405.10
VWF	XM_047429501.1	c.8116-20A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWF	ENST00000261405.10	c.8116-20A>C		intron_variant		1	NM_000552.5	P1
VWF	ENST00000612016.1	n.525-20A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25972 AN: 152010 Hom.: 2431 Cov.: 32

Gnomad AFR AF: 0.0922

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.187

GnomAD3 exomes AF: 0.194 AC: 48786 AN: 251342 Hom.: 5108 AF XY: 0.201 AC XY: 27291 AN XY: 135844

Gnomad AFR exome AF: 0.0918

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.195

Gnomad SAS exome AF: 0.228

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.208 AC: 304456 AN: 1460838 Hom.: 32613 Cov.: 33 AF XY: 0.210 AC XY: 152314 AN XY: 726784

Gnomad4 AFR exome AF: 0.0894

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.171 AC: 25981 AN: 152128 Hom.: 2428 Cov.: 32 AF XY: 0.169 AC XY: 12578 AN XY: 74368

Gnomad4 AFR AF: 0.0924

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.188

Alfa AF: 0.197 Hom.: 729

Bravo AF: 0.169

Asia WGS AF: 0.213 AC: 740 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.056
Dann	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2270152; hg19: chr12-6061069; COSMIC: COSV54611936; COSMIC: COSV54611936;