NM_000552.5:c.2821-607T>G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).
• 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

Gnomad4 AFR AF: 0.957

Gnomad4 AMR AF: 0.925

Gnomad4 ASJ AF: 0.941

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.879

Gnomad4 FIN AF: 0.897

Gnomad4 NFE AF: 0.909

Gnomad4 OTH AF: 0.922

Alfa AF: 0.914 Hom.: 57183

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

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: rs216318; hg19: chr12-6139261;