12-5991319-A-G

Variant names:

• chr12-5991319-A-G
• rs216893
• NM_000552.5:c.6798+500T>C

Variant summary

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

The NM_000552.5(VWF):​c.6798+500T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,910 control chromosomes in the GnomAD database, including 21,164 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 0.52 (21164 hom., cov: 31)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5	c.6798+500T>C		intron_variant	Intron 38 of 51	ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.6798+500T>C		intron_variant	Intron 38 of 51		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.6798+500T>C		intron_variant	Intron 38 of 51	1	NM_000552.5	ENSP00000261405.5

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79543 AN: 151792 Hom.: 21147 Cov.: 31

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.524 AC: 79599 AN: 151910 Hom.: 21164 Cov.: 31 AF XY: 0.527 AC XY: 39092 AN XY: 74234

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.524

Alfa AF: 0.530 Hom.: 2669

Bravo AF: 0.524

Asia WGS AF: 0.627 AC: 2181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.82

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: rs216893; hg19: chr12-6100485;