13-41885057-G-T

Variant names:

• chr13-41885057-G-T
• rs9566876
• NM_015058.2:c.975+863C>A

Variant summary

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

The NM_015058.2(VWA8):​c.975+863C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 151,986 control chromosomes in the GnomAD database, including 862 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 0.094 (862 hom., cov: 32)
• Consequence: VWA8 NM_015058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA8	NM_015058.2	c.975+863C>A		intron_variant	Intron 8 of 44	ENST00000379310.8	NP_055873.1
VWA8	NM_001009814.2	c.975+863C>A		intron_variant	Intron 8 of 25		NP_001009814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA8	ENST00000379310.8	c.975+863C>A		intron_variant	Intron 8 of 44	2	NM_015058.2	ENSP00000368612.3
VWA8	ENST00000281496.6	c.975+863C>A		intron_variant	Intron 8 of 25	1		ENSP00000281496.6

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14311 AN: 151868 Hom.: 859 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0629

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0567

Gnomad OTH AF: 0.0813

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

GnomAD4 genome AF: 0.0943 AC: 14329 AN: 151986 Hom.: 862 Cov.: 32 AF XY: 0.0916 AC XY: 6801 AN XY: 74262

African (AFR) AF: 0.174 AC: 7201 AN: 41406

American (AMR) AF: 0.0729 AC: 1114 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 358 AN: 3468

East Asian (EAS) AF: 0.136 AC: 705 AN: 5172

South Asian (SAS) AF: 0.0627 AC: 302 AN: 4814

European-Finnish (FIN) AF: 0.0531 AC: 559 AN: 10536

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0567 AC: 3853 AN: 67992

Other (OTH) AF: 0.0805 AC: 170 AN: 2112

Alfa AF: 0.0785 Hom.: 69

Bravo AF: 0.0981

Asia WGS AF: 0.0980 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.61
PhyloP100		-0.098
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: rs9566876; hg19: chr13-42459193;