12-6038839-T-C

Variant names:

• chr12-6038839-T-C
• rs216335
• NM_000552.5:c.2443-2348A>G

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VWF	NM_000552.5	c.2443-2348A>G		intron_variant	Intron 18 of 51	ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.2443-2348A>G		intron_variant	Intron 18 of 51		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.2443-2348A>G		intron_variant	Intron 18 of 51	1	NM_000552.5	ENSP00000261405.5
VWF	ENST00000538635.5	n.421-44905A>G		intron_variant	Intron 5 of 5	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

African (AFR) AF: 0.957 AC: 39778 AN: 41558

American (AMR) AF: 0.924 AC: 14142 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3220 AN: 3472

East Asian (EAS) AF: 0.792 AC: 4106 AN: 5182

South Asian (SAS) AF: 0.876 AC: 4217 AN: 4816

European-Finnish (FIN) AF: 0.897 AC: 9515 AN: 10608

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61792 AN: 68036

Other (OTH) AF: 0.920 AC: 1945 AN: 2114

Alfa AF: 0.914 Hom.: 105394

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
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

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Other links and lift over

dbSNP: rs216335; hg19: chr12-6148005;