13-41725517-G-C

Variant names:

• chr13-41725517-G-C
• rs9590631
• NM_015058.2:c.2758+1677C>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.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
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 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.2758+1677C>G		intron	N/A	NP_055873.1
	VWA8	NM_001009814.2		c.2758+1677C>G		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.2758+1677C>G		intron	N/A	ENSP00000368612.3
	VWA8	ENST00000281496.6	TSL:1	c.2758+1677C>G		intron	N/A	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

African (AFR) AF: 0.0928 AC: 3852 AN: 41516

American (AMR) AF: 0.307 AC: 4691 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1350 AN: 3468

East Asian (EAS) AF: 0.215 AC: 1115 AN: 5176

South Asian (SAS) AF: 0.306 AC: 1474 AN: 4812

European-Finnish (FIN) AF: 0.323 AC: 3415 AN: 10562

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22477 AN: 67966

Other (OTH) AF: 0.271 AC: 572 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.84
DANN	Benign	0.39
PhyloP100		-0.68
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: rs9590631; hg19: chr13-42299653;