rs216295

Variant names:

• chr12-6045040-T-C
• rs216295
• NM_000552.5:c.2282-589A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000552.5(VWF):​c.2282-589A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,170 control chromosomes in the GnomAD database, including 58,351 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 0.87 (58351 hom., cov: 32)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5	c.2282-589A>G		intron_variant	Intron 17 of 51	ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.2282-589A>G		intron_variant	Intron 17 of 51		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.2282-589A>G		intron_variant	Intron 17 of 51	1	NM_000552.5	ENSP00000261405.5
VWF	ENST00000538635.5	n.421-51106A>G		intron_variant	Intron 5 of 5	4

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132967 AN: 152052 Hom.: 58320 Cov.: 32

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.901

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

GnomAD4 genome AF: 0.874 AC: 133055 AN: 152170 Hom.: 58351 Cov.: 32 AF XY: 0.875 AC XY: 65095 AN XY: 74398

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.906

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.891

Gnomad4 NFE AF: 0.904

Gnomad4 OTH AF: 0.895

Alfa AF: 0.891 Hom.: 16891

Bravo AF: 0.874

Asia WGS AF: 0.840 AC: 2922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.56

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: rs216295; hg19: chr12-6154206;