Variant chr7-12375099-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001135924.3(VWDE):c.1153C>T(p.Arg385Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,550,886 control chromosomes in the GnomAD database, including 13,149 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. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.14 ( 1619 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11530 hom. )

Consequence

VWDE
NM_001135924.3 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

Variant links:

Genes affected

VWDE (HGNC:21897): (von Willebrand factor D and EGF domains) Predicted to enable signaling receptor binding activity. Predicted to be involved in anatomical structure development. Predicted to be active in cell surface and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

VWDE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VWDE	NM_001135924.3 linkuse as main transcript	c.1153C>T	p.Arg385Ter	stop_gained	8/29	ENST00000275358.8	NP_001129396.1
VWDE	NM_001346972.2 linkuse as main transcript	c.1153C>T	p.Arg385Ter	stop_gained	8/27		NP_001333901.1
VWDE	NM_001346973.2 linkuse as main transcript	c.688C>T	p.Arg230Ter	stop_gained	8/27		NP_001333902.1
VWDE	NR_144534.2 linkuse as main transcript	n.1302C>T		non_coding_transcript_exon_variant	8/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWDE	ENST00000275358.8 linkuse as main transcript	c.1153C>T	p.Arg385Ter	stop_gained	8/29	5	NM_001135924.3	ENSP00000275358	P1	Q8N2E2-1
VWDE	ENST00000452576.6 linkuse as main transcript	c.1153C>T	p.Arg385Ter	stop_gained, NMD_transcript_variant	8/30	1		ENSP00000401687
VWDE	ENST00000521169.5 linkuse as main transcript	c.1024+2677C>T		intron_variant, NMD_transcript_variant		5		ENSP00000428810

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20675

AN:

151890

Hom.:

1618

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.0787

Gnomad ASJ

AF:

0.0866

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.124

AC:

19531

AN:

156890

Hom.:

1441

AF XY:

0.130

AC XY:

10823

AN XY:

83028

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.0571

Gnomad ASJ exome

AF:

0.0947

Gnomad EAS exome

AF:

0.196

Gnomad SAS exome

AF:

0.192

Gnomad FIN exome

AF:

0.112

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.0979

GnomAD4 exome

AF:

0.124

AC:

172887

AN:

1398878

Hom.:

11530

Cov.:

AF XY:

0.125

AC XY:

86490

AN XY:

689944

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.0620

Gnomad4 ASJ exome

AF:

0.0902

Gnomad4 EAS exome

AF:

0.218

Gnomad4 SAS exome

AF:

0.194

Gnomad4 FIN exome

AF:

0.113

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.136

AC:

20693

AN:

152008

Hom.:

1619

Cov.:

AF XY:

0.137

AC XY:

10181

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.0787

Gnomad4 ASJ

AF:

0.0866

Gnomad4 EAS

AF:

0.195

Gnomad4 SAS

AF:

0.205

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.117

Hom.:

2145

Bravo

AF:

0.135

TwinsUK

AF:

0.112

AC:

416

ALSPAC

AF:

0.122

AC:

471

ESP6500AA

AF:

0.209

AC:

289

ESP6500EA

AF:

0.114

AC:

362

ExAC

AF:

0.141

AC:

3476

Asia WGS

AF:

0.178

AC:

617

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.061

FATHMM_MKL

Benign

0.28

MutationTaster

Benign

2.7e-24

Vest4

0.070

GERP RS

3.8

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over