rs216318

Variant names:

• chr12-6030095-A-C
• rs216318
• NM_000552.5:c.2821-607T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-6030095-A-C
• chr12-6030095-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000552.5(VWF):​c.2821-607T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.919 in 152,224 control chromosomes in the GnomAD database, including 64,408 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 0.92 (64408 hom., cov: 32)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5	c.2821-607T>G		intron_variant	Intron 21 of 51	ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.2821-607T>G		intron_variant	Intron 21 of 51		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.2821-607T>G		intron_variant	Intron 21 of 51	1	NM_000552.5	ENSP00000261405.5
VWF	ENST00000538635.5	n.421-36161T>G		intron_variant	Intron 5 of 5	4

Frequencies

GnomAD3 genomes AF: 0.919 AC: 139773 AN: 152106 Hom.: 64352 Cov.: 32

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.925

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.897

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.928

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

GnomAD4 genome AF: 0.919 AC: 139886 AN: 152224 Hom.: 64408 Cov.: 32 AF XY: 0.918 AC XY: 68307 AN XY: 74428

African (AFR) AF: 0.957 AC: 39775 AN: 41546

American (AMR) AF: 0.925 AC: 14142 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3268 AN: 3472

East Asian (EAS) AF: 0.795 AC: 4107 AN: 5166

South Asian (SAS) AF: 0.879 AC: 4231 AN: 4814

European-Finnish (FIN) AF: 0.897 AC: 9507 AN: 10600

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.909 AC: 61794 AN: 68016

Other (OTH) AF: 0.922 AC: 1948 AN: 2112

Alfa AF: 0.917 Hom.: 77111

Bravo AF: 0.924

Asia WGS AF: 0.846 AC: 2944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.5
DANN	Benign	0.45
PhyloP100		0.36
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: rs216318; hg19: chr12-6139261;