12-6077501-A-G

Variant names:

• chr12-6077501-A-G
• rs2239153
• NM_000552.5:c.658-1950T>C

Variant summary

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

The NM_000552.5(VWF):​c.658-1950T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,700 control chromosomes in the GnomAD database, including 23,134 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 0.53 (23134 hom., cov: 33)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5	c.658-1950T>C		intron_variant	Intron 6 of 51	ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.658-1950T>C		intron_variant	Intron 6 of 51		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.658-1950T>C		intron_variant	Intron 6 of 51	1	NM_000552.5	ENSP00000261405.5
VWF	ENST00000538635.5	n.420+33014T>C		intron_variant	Intron 5 of 5	4

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81084 AN: 151582 Hom.: 23103 Cov.: 33

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.535 AC: 81149 AN: 151700 Hom.: 23134 Cov.: 33 AF XY: 0.529 AC XY: 39256 AN XY: 74140

Gnomad4 AFR AF: 0.737

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.502

Alfa AF: 0.495 Hom.: 2696

Bravo AF: 0.547

Asia WGS AF: 0.368 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.23

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: rs2239153; hg19: chr12-6186667;