rs2270151

chr12-5951794-G-A

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.8155+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,602,898 control chromosomes in the GnomAD database, including 18,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1352 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16974 hom.)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.327

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=-0.9).
• BP6: Variant 12-5951794-G-A is Benign according to our data. Variant chr12-5951794-G-A is described in ClinVar as [Benign]. Clinvar id is 256704.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWF	NM_000552.5	c.8155+50C>T		intron_variant		ENST00000261405.10
VWF	XM_047429501.1	c.8155+50C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWF	ENST00000261405.10	c.8155+50C>T		intron_variant		1	NM_000552.5	P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18992 AN: 152106 Hom.: 1352 Cov.: 32

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0998

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.142

GnomAD3 exomes AF: 0.134 AC: 33804 AN: 251340 Hom.: 2563 AF XY: 0.136 AC XY: 18543 AN XY: 135856

Gnomad AFR exome AF: 0.0703

Gnomad AMR exome AF: 0.0781

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.191

Gnomad SAS exome AF: 0.103

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.149 AC: 216698 AN: 1450674 Hom.: 16974 Cov.: 29 AF XY: 0.149 AC XY: 107294 AN XY: 722370

Gnomad4 AFR exome AF: 0.0692

Gnomad4 AMR exome AF: 0.0817

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.117

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.125 AC: 18997 AN: 152224 Hom.: 1352 Cov.: 32 AF XY: 0.123 AC XY: 9156 AN XY: 74432

Gnomad4 AFR AF: 0.0704

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.143

Alfa AF: 0.154 Hom.: 2636

Bravo AF: 0.126

Asia WGS AF: 0.158 AC: 549 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	-0.90
Cadd	Benign	2.0
Dann	Benign	0.47

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: rs2270151; hg19: chr12-6060960; COSMIC: COSV54611921; COSMIC: COSV54611921;