rs9590631

Positions:

• chr13-41725517-G-C
• chr13-41725517-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015058.2(VWA8):​c.2758+1677C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,096 control chromosomes in the GnomAD database, including 5,924 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 0.26 (5924 hom., cov: 32)
• Consequence: VWA8 NM_015058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA8	NM_015058.2	c.2758+1677C>G		intron_variant		ENST00000379310.8	NP_055873.1
VWA8	NM_001009814.2	c.2758+1677C>G		intron_variant			NP_001009814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA8	ENST00000379310.8	c.2758+1677C>G		intron_variant		2	NM_015058.2	ENSP00000368612.3
VWA8	ENST00000281496.6	c.2758+1677C>G		intron_variant		1		ENSP00000281496.6

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39214 AN: 151976 Hom.: 5928 Cov.: 32

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.258 AC: 39211 AN: 152096 Hom.: 5924 Cov.: 32 AF XY: 0.261 AC XY: 19370 AN XY: 74322

Gnomad4 AFR AF: 0.0928

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.271

Alfa AF: 0.161 Hom.: 329

Bravo AF: 0.251

Asia WGS AF: 0.217 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.84
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs9590631; hg19: chr13-42299653;