chr12-6023913-T-C

Position:

• chr12-6023913-T-C

Variant summary

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

The NM_000552.5(VWF):​c.3223-126A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 1,010,306 control chromosomes in the GnomAD database, including 4,098 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 0.089 (617 hom., cov: 32)
  • Exomes 𝑓: 0.085 (3481 hom.)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWF	NM_000552.5	c.3223-126A>G		intron_variant		ENST00000261405.10
VWF	XM_047429501.1	c.3223-126A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWF	ENST00000261405.10	c.3223-126A>G		intron_variant		1	NM_000552.5	P1
VWF	ENST00000538635.5	n.421-29979A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0889 AC: 13537 AN: 152192 Hom.: 618 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0656

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0753

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0807

Gnomad OTH AF: 0.0935

GnomAD4 exome AF: 0.0853 AC: 73204 AN: 857996 Hom.: 3481 AF XY: 0.0884 AC XY: 39082 AN XY: 442222

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.0506

Gnomad4 ASJ exome AF: 0.0500

Gnomad4 EAS exome AF: 0.110

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.0751

Gnomad4 NFE exome AF: 0.0797

Gnomad4 OTH exome AF: 0.0848

GnomAD4 genome AF: 0.0889 AC: 13540 AN: 152310 Hom.: 617 Cov.: 32 AF XY: 0.0901 AC XY: 6708 AN XY: 74476

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0655

Gnomad4 ASJ AF: 0.0504

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0753

Gnomad4 NFE AF: 0.0807

Gnomad4 OTH AF: 0.0930

Alfa AF: 0.0788 Hom.: 70

Bravo AF: 0.0875

Asia WGS AF: 0.116 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.026
DANN	Benign	0.83

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: rs2854871; hg19: chr12-6133079;