chr3-184879292-A-G

Variant names:

• chr3-184879292-A-G
• rs11717139
• NM_001009921.3:c.1735-6818A>G

Variant summary

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

The NM_001009921.3(VPS8):​c.1735-6818A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,120 control chromosomes in the GnomAD database, including 4,983 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 0.23 (4983 hom., cov: 32)
• Consequence: VPS8 NM_001009921.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.467
• Publications: 3 publications found

Genes affected

VPS8 (HGNC:29122): (VPS8 subunit of CORVET complex) Predicted to enable metal ion binding activity. Involved in endosomal vesicle fusion. Located in early endosome. [provided by Alliance of Genome Resources, Apr 2022]

VPS8 Gene-Disease associations (from GenCC):

• arthrogryposis multiplex congenita

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS8	NM_001009921.3	c.1735-6818A>G		intron_variant	Intron 21 of 47	ENST00000625842.3	NP_001009921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS8	ENST00000625842.3	c.1735-6818A>G		intron_variant	Intron 21 of 47	5	NM_001009921.3	ENSP00000487164.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35517 AN: 152000 Hom.: 4981 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.234 AC: 35540 AN: 152120 Hom.: 4983 Cov.: 32 AF XY: 0.248 AC XY: 18401 AN XY: 74342

African (AFR) AF: 0.145 AC: 6041 AN: 41520

American (AMR) AF: 0.327 AC: 4999 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 771 AN: 3466

East Asian (EAS) AF: 0.626 AC: 3225 AN: 5150

South Asian (SAS) AF: 0.414 AC: 1996 AN: 4824

European-Finnish (FIN) AF: 0.335 AC: 3539 AN: 10568

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14236 AN: 67990

Other (OTH) AF: 0.240 AC: 507 AN: 2110

Alfa AF: 0.226 Hom.: 2191

Bravo AF: 0.226

Asia WGS AF: 0.463 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.73
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: rs11717139; hg19: chr3-184597080;