rs216805

chr12-6002310-A-Gchr12-6002310-A-T

Variant summary

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

The NM_000552.5(VWF):c.5843-6088T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,644 control chromosomes in the GnomAD database, including 7,289 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 0.30 (7289 hom., cov: 32)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWF	NM_000552.5	c.5843-6088T>C		intron_variant		ENST00000261405.10
VWF	XM_047429501.1	c.5843-6088T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWF	ENST00000261405.10	c.5843-6088T>C		intron_variant		1	NM_000552.5	P1
VWF	ENST00000538635.5	n.421-8376T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45027 AN: 151520 Hom.: 7268 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.297 AC: 45096 AN: 151644 Hom.: 7289 Cov.: 32 AF XY: 0.304 AC XY: 22523 AN XY: 74118

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.300

Alfa AF: 0.172 Hom.: 376

Bravo AF: 0.304

Asia WGS AF: 0.430 AC: 1466 AN: 3408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	3.8
Dann	Benign	0.55

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: rs216805; hg19: chr12-6111476; COSMIC: COSV54612461;