Variant 13-41960845-C-T 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.163+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,517,228 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0080 ( 21 hom., cov: 32)

Exomes 𝑓: 0.00081 ( 19 hom. )

Consequence

VWA8
NM_015058.2 splice_region, intron

Scores

Splicing: ADA: 0.0003400

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.412

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:

VWA8-AS1 (HGNC:):

VWA8-AS1 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 (BayesDel_noAF=-0.57).

BP6

Variant 13-41960845-C-T is Benign according to our data. Variant chr13-41960845-C-T is described in ClinVar as [Benign]. Clinvar id is 789634.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.008 (1219/152332) while in subpopulation AFR AF= 0.0276 (1147/41574). AF 95% confidence interval is 0.0263. There are 21 homozygotes in gnomad4. There are 574 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1219 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA8	NM_015058.2 linkuse as main transcript	c.163+8G>A		splice_region_variant, intron_variant		ENST00000379310.8	NP_055873.1	A3KMH1-1
VWA8	NM_001009814.2 linkuse as main transcript	c.163+8G>A		splice_region_variant, intron_variant			NP_001009814.1	A3KMH1-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
VWA8	ENST00000379310.8 linkuse as main transcript	c.163+8G>A	splice_region_variant, intron_variant	2	NM_015058.2	ENSP00000368612.3	A3KMH1-1
VWA8	ENST00000281496.6 linkuse as main transcript	c.163+8G>A	splice_region_variant, intron_variant	1		ENSP00000281496.6	A3KMH1-2
VWA8-AS1	ENST00000612345.4 linkuse as main transcript	n.71+4967C>T	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00798

AC:

1215

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0276

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00124

AC:

140

AN:

112792

Hom.:

AF XY:

0.000988

AC XY:

AN XY:

62746

show subpopulations

Gnomad AFR exome

AF:

0.0300

Gnomad AMR exome

AF:

0.00144

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000184

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.000815

AC:

1112

AN:

1364896

Hom.:

Cov.:

AF XY:

0.000686

AC XY:

462

AN XY:

673868

show subpopulations

Gnomad4 AFR exome

AF:

0.0314

Gnomad4 AMR exome

AF:

0.00189

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000765

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000383

Gnomad4 OTH exome

AF:

0.00176

GnomAD4 genome

AF:

0.00800

AC:

1219

AN:

152332

Hom.:

Cov.:

AF XY:

0.00771

AC XY:

574

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0276

Gnomad4 AMR

AF:

0.00372

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00401

Hom.:

Bravo

AF:

0.00876

Asia WGS

AF:

0.00231

AC:

AN:

3478

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

Labcorp Genetics (formerly Invitae), Labcorp

Feb 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.3

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00034

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over