13-41889697-C-T

Variant names:

• chr13-41889697-C-T
• rs10507501
• NM_015058.2:c.651+1723G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015058.2(VWA8):​c.651+1723G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 152,102 control chromosomes in the GnomAD database, including 395 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 0.064 (395 hom., cov: 32)
• Consequence: VWA8 NM_015058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 97

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

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 (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA8	NM_015058.2	c.651+1723G>A		intron_variant	Intron 5 of 44	ENST00000379310.8	NP_055873.1
VWA8	NM_001009814.2	c.651+1723G>A		intron_variant	Intron 5 of 25		NP_001009814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA8	ENST00000379310.8	c.651+1723G>A		intron_variant	Intron 5 of 44	2	NM_015058.2	ENSP00000368612.3
VWA8	ENST00000281496.6	c.651+1723G>A		intron_variant	Intron 5 of 25	1		ENSP00000281496.6

Frequencies

GnomAD3 genomes AF: 0.0644 AC: 9784 AN: 151984 Hom.: 390 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0566

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.0337

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0576

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0645 AC: 9804 AN: 152102 Hom.: 395 Cov.: 32 AF XY: 0.0631 AC XY: 4696 AN XY: 74386

African (AFR) AF: 0.110 AC: 4543 AN: 41468

American (AMR) AF: 0.0571 AC: 872 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3470

East Asian (EAS) AF: 0.114 AC: 591 AN: 5166

South Asian (SAS) AF: 0.0433 AC: 209 AN: 4826

European-Finnish (FIN) AF: 0.0337 AC: 357 AN: 10606

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0400 AC: 2718 AN: 67976

Other (OTH) AF: 0.0570 AC: 120 AN: 2106

Alfa AF: 0.0225 Hom.: 21

Bravo AF: 0.0680

Asia WGS AF: 0.0830 AC: 287 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	3.9
DANN	Benign	0.60
PhyloP100		0.25
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

Other links and lift over

dbSNP: rs10507501; hg19: chr13-42463833;