NM_015058.2:c.4986+3716C>G

Variant names:

• chr13-41601452-G-C
• rs9590614
• NM_015058.2:c.4986+3716C>G

Variant summary

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

The NM_015058.2(VWA8):​c.4986+3716C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,972 control chromosomes in the GnomAD database, including 7,963 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 0.31 (7963 hom., cov: 32)
• Consequence: VWA8 NM_015058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 10 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)

ENSG00000288598 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA8	NM_015058.2	c.4986+3716C>G		intron_variant	Intron 40 of 44	ENST00000379310.8	NP_055873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA8	ENST00000379310.8	c.4986+3716C>G		intron_variant	Intron 40 of 44	2	NM_015058.2	ENSP00000368612.3
ENSG00000288598	ENST00000842280.1	n.589-1303G>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46851 AN: 151854 Hom.: 7962 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.308 AC: 46851 AN: 151972 Hom.: 7963 Cov.: 32 AF XY: 0.309 AC XY: 22963 AN XY: 74288

African (AFR) AF: 0.162 AC: 6715 AN: 41472

American (AMR) AF: 0.328 AC: 5013 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1425 AN: 3472

East Asian (EAS) AF: 0.169 AC: 871 AN: 5156

South Asian (SAS) AF: 0.359 AC: 1729 AN: 4822

European-Finnish (FIN) AF: 0.370 AC: 3902 AN: 10550

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26167 AN: 67922

Other (OTH) AF: 0.322 AC: 678 AN: 2108

Alfa AF: 0.222 Hom.: 525

Bravo AF: 0.298

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.8
DANN	Benign	0.71
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9590614; hg19: chr13-42175588;