Variant 13-41685059-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015058.2(VWA8):c.4315A>C(p.Ile1439Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00752 in 1,612,892 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 25 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 83 hom. )

Consequence

VWA8
NM_015058.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.382

Variant links:

Genes affected

VWA8 (HGNC:29071): (von Willebrand factor A domain containing 8) Predicted to enable ATP binding activity. Located in mitochondrion and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

VWA8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032001436).

BP6

Variant 13-41685059-T-G is Benign according to our data. Variant chr13-41685059-T-G is described in ClinVar as [Benign]. Clinvar id is 770991.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2195/152304) while in subpopulation AFR AF= 0.0387 (1610/41554). AF 95% confidence interval is 0.0372. There are 25 homozygotes in gnomad4. There are 1055 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2195 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWA8	NM_015058.2 linkuse as main transcript	c.4315A>C	p.Ile1439Leu	missense_variant	35/45	ENST00000379310.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWA8	ENST00000379310.8 linkuse as main transcript	c.4315A>C	p.Ile1439Leu	missense_variant	35/45	2	NM_015058.2	P1	A3KMH1-1

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2188

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00655

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0162

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00510

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00858

AC:

2133

AN:

248602

Hom.:

AF XY:

0.00866

AC XY:

1168

AN XY:

134874

show subpopulations

Gnomad AFR exome

AF:

0.0398

Gnomad AMR exome

AF:

0.00471

Gnomad ASJ exome

AF:

0.00279

Gnomad EAS exome

AF:

0.000948

Gnomad SAS exome

AF:

0.0193

Gnomad FIN exome

AF:

0.00232

Gnomad NFE exome

AF:

0.00553

Gnomad OTH exome

AF:

0.00830

GnomAD4 exome

AF:

0.00680

AC:

9933

AN:

1460588

Hom.:

Cov.:

AF XY:

0.00719

AC XY:

5225

AN XY:

726596

show subpopulations

Gnomad4 AFR exome

AF:

0.0419

Gnomad4 AMR exome

AF:

0.00459

Gnomad4 ASJ exome

AF:

0.00245

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0193

Gnomad4 FIN exome

AF:

0.00268

Gnomad4 NFE exome

AF:

0.00531

Gnomad4 OTH exome

AF:

0.00802

GnomAD4 genome

AF:

0.0144

AC:

2195

AN:

152304

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1055

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0387

Gnomad4 AMR

AF:

0.00654

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0164

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00510

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00722

Hom.:

Bravo

AF:

0.0160

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.0362

AC:

131

ESP6500EA

AF:

0.00564

AC:

ExAC

AF:

0.00958

AC:

1157

Asia WGS

AF:

0.0170

AC:

AN:

3476

EpiCase

AF:

0.00551

EpiControl

AF:

0.00718

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.018

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.74

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.37

REVEL

Benign

0.073

Sift

Benign

0.44

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.38

MVP

0.014

MPC

0.056

ClinPred

0.0020

GERP RS

2.6

Varity_R

0.069

gMVP

0.44

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over