rs7306706

chr12-6106468-A-Gchr12-6106468-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.532+3906T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,088 control chromosomes in the GnomAD database, including 30,118 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 0.60 (30118 hom., cov: 32)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWF	NM_000552.5	c.532+3906T>C		intron_variant		ENST00000261405.10
VWF	XM_047429501.1	c.532+3906T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWF	ENST00000261405.10	c.532+3906T>C		intron_variant		1	NM_000552.5	P1
VWF	ENST00000321023.5	c.*591+3906T>C		intron_variant, NMD_transcript_variant		1
VWF	ENST00000538635.5	n.420+4047T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90620 AN: 151970 Hom.: 30044 Cov.: 32

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.597 AC: 90758 AN: 152088 Hom.: 30118 Cov.: 32 AF XY: 0.598 AC XY: 44449 AN XY: 74330

Gnomad4 AFR AF: 0.895

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.595

Alfa AF: 0.466 Hom.: 22058

Bravo AF: 0.621

Asia WGS AF: 0.710 AC: 2465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.3
Dann	Benign	0.67

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: rs7306706; hg19: chr12-6215634;