rs9566845

Variant names:

• chr13-41761944-G-A
• rs9566845
• NM_015058.2:c.2350-740C>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.2350-740C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 151,996 control chromosomes in the GnomAD database, including 354 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 (354 hom., cov: 32)
• Consequence: VWA8 NM_015058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA8	NM_015058.2	c.2350-740C>T		intron_variant	Intron 20 of 44	ENST00000379310.8	NP_055873.1
VWA8	NM_001009814.2	c.2350-740C>T		intron_variant	Intron 20 of 25		NP_001009814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA8	ENST00000379310.8	c.2350-740C>T		intron_variant	Intron 20 of 44	2	NM_015058.2	ENSP00000368612.3
VWA8	ENST00000281496.6	c.2350-740C>T		intron_variant	Intron 20 of 25	1		ENSP00000281496.6

Frequencies

GnomAD3 genomes AF: 0.0609 AC: 9254 AN: 151878 Hom.: 349 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0548

Gnomad ASJ AF: 0.0904

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0396

Gnomad OTH AF: 0.0546

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

GnomAD4 genome AF: 0.0610 AC: 9266 AN: 151996 Hom.: 354 Cov.: 32 AF XY: 0.0598 AC XY: 4441 AN XY: 74316

African (AFR) AF: 0.0989 AC: 4092 AN: 41358

American (AMR) AF: 0.0552 AC: 843 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0904 AC: 313 AN: 3464

East Asian (EAS) AF: 0.112 AC: 581 AN: 5180

South Asian (SAS) AF: 0.0460 AC: 222 AN: 4824

European-Finnish (FIN) AF: 0.0336 AC: 356 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0396 AC: 2693 AN: 67990

Other (OTH) AF: 0.0540 AC: 114 AN: 2110

Alfa AF: 0.0526 Hom.: 36

Bravo AF: 0.0638

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.41
DANN	Benign	0.49
PhyloP100		-0.87
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: rs9566845; hg19: chr13-42336080;