rs17700752

Positions:

• chr7-38786735-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014396.4(VPS41):​c.784+3066T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,980 control chromosomes in the GnomAD database, including 5,282 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 0.25 (5282 hom., cov: 31)
• Consequence: VPS41 NM_014396.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.835

Genes affected

VPS41 (HGNC:12713): (VPS41 subunit of HOPS complex) 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 ortholog of yeast Vps41 protein which is also conserved in Drosophila, tomato, and Arabidopsis. Expression studies in yeast and human indicate that this protein may be involved in the formation and fusion of transport vesicles from the Golgi. Several transcript variants encoding different isoforms have been described for this gene, however, the full-length nature of not all is known. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS41	NM_014396.4	c.784+3066T>C		intron_variant		ENST00000310301.9	NP_055211.2
VPS41	NM_080631.4	c.709+3066T>C		intron_variant			NP_542198.2
VPS41	XR_007060008.1	n.801+3066T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS41	ENST00000310301.9	c.784+3066T>C		intron_variant		1	NM_014396.4	ENSP00000309457	P1
VPS41	ENST00000395969.6	c.709+3066T>C		intron_variant		5		ENSP00000379297
VPS41	ENST00000466017.1	n.324+3066T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38169 AN: 151862 Hom.: 5278 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.251 AC: 38204 AN: 151980 Hom.: 5282 Cov.: 31 AF XY: 0.258 AC XY: 19143 AN XY: 74276

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.233

Alfa AF: 0.212 Hom.: 1841

Bravo AF: 0.258

Asia WGS AF: 0.404 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.2
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs17700752; hg19: chr7-38826335;