13-41854763-G-A

Variant names:

• chr13-41854763-G-A
• rs9566867
• NM_015058.2:c.1425+10973C>T

Variant summary

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

The NM_015058.2(VWA8):​c.1425+10973C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 152,268 control chromosomes in the GnomAD database, including 359 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 0.061 (359 hom., cov: 31)
• Consequence: VWA8 NM_015058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470
• 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=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015058.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA8	NM_015058.2	MANE Select	c.1425+10973C>T		intron	N/A	NP_055873.1
	VWA8	NM_001009814.2		c.1425+10973C>T		intron	N/A	NP_001009814.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA8	ENST00000379310.8	TSL:2 MANE Select	c.1425+10973C>T		intron	N/A	ENSP00000368612.3
	VWA8	ENST00000281496.6	TSL:1	c.1425+10973C>T		intron	N/A	ENSP00000281496.6

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 9309 AN: 152150 Hom.: 354 Cov.: 31

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.0913

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0398

Gnomad OTH AF: 0.0556

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

GnomAD4 genome AF: 0.0612 AC: 9323 AN: 152268 Hom.: 359 Cov.: 31 AF XY: 0.0600 AC XY: 4470 AN XY: 74454

African (AFR) AF: 0.0997 AC: 4145 AN: 41554

American (AMR) AF: 0.0559 AC: 854 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 317 AN: 3472

East Asian (EAS) AF: 0.115 AC: 598 AN: 5190

South Asian (SAS) AF: 0.0381 AC: 184 AN: 4830

European-Finnish (FIN) AF: 0.0332 AC: 352 AN: 10598

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0398 AC: 2705 AN: 68022

Other (OTH) AF: 0.0550 AC: 116 AN: 2110

Alfa AF: 0.0508 Hom.: 355

Bravo AF: 0.0644

Asia WGS AF: 0.0790 AC: 273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		0.47
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: rs9566867; hg19: chr13-42428899;