rs7306706

Variant names:

• chr12-6106468-A-G
• rs7306706
• NM_000552.5:c.532+3906T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-6106468-A-G
• chr12-6106468-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

VWF Gene-Disease associations (from GenCC):

• hereditary von Willebrand disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• von Willebrand disease type 2B

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• von Willebrand disease 2

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• von Willebrand disease 1

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• von Willebrand disease type 2A

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• von Willebrand disease type 2M

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• von Willebrand disease 3

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• von Willebrand disease type 2N

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VWF	NM_000552.5	c.532+3906T>C		intron_variant	Intron 5 of 51	ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.532+3906T>C		intron_variant	Intron 5 of 51		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.532+3906T>C		intron_variant	Intron 5 of 51	1	NM_000552.5	ENSP00000261405.5
VWF	ENST00000321023.5	n.*591+3906T>C		intron_variant	Intron 6 of 6	1		ENSP00000461331.1
VWF	ENST00000538635.5	n.420+4047T>C		intron_variant	Intron 5 of 5	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

African (AFR) AF: 0.895 AC: 37146 AN: 41524

American (AMR) AF: 0.609 AC: 9308 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1854 AN: 3470

East Asian (EAS) AF: 0.696 AC: 3603 AN: 5174

South Asian (SAS) AF: 0.627 AC: 3018 AN: 4816

European-Finnish (FIN) AF: 0.437 AC: 4615 AN: 10560

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29353 AN: 67958

Other (OTH) AF: 0.595 AC: 1254 AN: 2106

Alfa AF: 0.478 Hom.: 32343

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7306706; hg19: chr12-6215634;