rs9532931

Variant names:

• chr13-41825943-T-C
• rs9532931
• NM_015058.2:c.1700+4586A>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.1700+4586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0842 in 152,254 control chromosomes in the GnomAD database, including 556 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 0.084 (556 hom., cov: 32)
• Consequence: VWA8 NM_015058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• Publications: 5 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA8	NM_015058.2	c.1700+4586A>G		intron_variant	Intron 14 of 44	ENST00000379310.8	NP_055873.1
VWA8	NM_001009814.2	c.1700+4586A>G		intron_variant	Intron 14 of 25		NP_001009814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA8	ENST00000379310.8	c.1700+4586A>G		intron_variant	Intron 14 of 44	2	NM_015058.2	ENSP00000368612.3
VWA8	ENST00000281496.6	c.1700+4586A>G		intron_variant	Intron 14 of 25	1		ENSP00000281496.6

Frequencies

GnomAD3 genomes AF: 0.0841 AC: 12802 AN: 152136 Hom.: 554 Cov.: 32

Gnomad AFR AF: 0.0958

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0680

Gnomad ASJ AF: 0.0877

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0975

Gnomad FIN AF: 0.0572

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.0923

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

GnomAD4 genome AF: 0.0842 AC: 12814 AN: 152254 Hom.: 556 Cov.: 32 AF XY: 0.0836 AC XY: 6225 AN XY: 74440

African (AFR) AF: 0.0957 AC: 3975 AN: 41538

American (AMR) AF: 0.0679 AC: 1038 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0877 AC: 304 AN: 3468

East Asian (EAS) AF: 0.110 AC: 567 AN: 5178

South Asian (SAS) AF: 0.0978 AC: 472 AN: 4826

European-Finnish (FIN) AF: 0.0572 AC: 607 AN: 10614

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0814 AC: 5540 AN: 68022

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

Alfa AF: 0.0828 Hom.: 955

Bravo AF: 0.0849

Asia WGS AF: 0.116 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		0.32
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: rs9532931; hg19: chr13-42400079;