rs8036080

Variant names:

• chr15-40904186-G-A
• rs8036080
• NM_020857.3:c.*845G>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_020857.3(VPS18):​c.*845G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 152,262 control chromosomes in the GnomAD database, including 50 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 0.019 (50 hom., cov: 32)
• Consequence: VPS18 NM_020857.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

Genes affected

VPS18 (HGNC:15972): (VPS18 core subunit of CORVET and HOPS complexes) Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human homolog of yeast class C Vps18 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0188 (2865/152262) while in subpopulation NFE AF= 0.0293 (1995/67994). AF 95% confidence interval is 0.0283. There are 50 homozygotes in gnomad4. There are 1352 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2865 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS18	NM_020857.3	c.*845G>A		downstream_gene_variant		ENST00000220509.10	NP_065908.1
VPS18	XM_011521843.3	c.*845G>A		downstream_gene_variant			XP_011520145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS18	ENST00000220509.10	c.*845G>A		downstream_gene_variant		1	NM_020857.3	ENSP00000220509.5

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2866 AN: 152144 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.00405

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0294

Gnomad OTH AF: 0.0129

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

GnomAD4 genome AF: 0.0188 AC: 2865 AN: 152262 Hom.: 50 Cov.: 32 AF XY: 0.0182 AC XY: 1352 AN XY: 74460

Gnomad4 AFR AF: 0.00404

Gnomad4 AMR AF: 0.0125

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.0372

Gnomad4 NFE AF: 0.0293

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0247 Hom.: 46

Bravo AF: 0.0161

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8036080; hg19: chr15-41196384;