rs216335

chr12-6038839-T-Cchr12-6038839-T-G

Variant summary

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

The NM_000552.5(VWF):c.2443-2348A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 152,294 control chromosomes in the GnomAD database, including 64,321 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 (64321 hom., cov: 32)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.937

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=-0.9).
• 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/exons	MANE	UniProt
VWF	NM_000552.5	c.2443-2348A>G		intron_variant		ENST00000261405.10
VWF	XM_047429501.1	c.2443-2348A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWF	ENST00000261405.10	c.2443-2348A>G		intron_variant		1	NM_000552.5	P1
VWF	ENST00000538635.5	n.421-44905A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139710 AN: 152176 Hom.: 64265 Cov.: 32

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.897

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.925

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

GnomAD4 genome AF: 0.918 AC: 139824 AN: 152294 Hom.: 64321 Cov.: 32 AF XY: 0.917 AC XY: 68259 AN XY: 74446

Gnomad4 AFR AF: 0.957

Gnomad4 AMR AF: 0.924

Gnomad4 ASJ AF: 0.927

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.876

Gnomad4 FIN AF: 0.897

Gnomad4 NFE AF: 0.908

Gnomad4 OTH AF: 0.920

Alfa AF: 0.912 Hom.: 82782

Bravo AF: 0.923

Asia WGS AF: 0.839 AC: 2919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.75
Dann	Benign	0.47

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: rs216335; hg19: chr12-6148005;