ENST00000457055.1:c.-130+1441A>G

Variant names:

• chr7-38930837-T-C
• rs17171485
• ENST00000457055.1:c.-130+1441A>G

Variant summary

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

The ENST00000457055.1(VPS41):​c.-130+1441A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 152,264 control chromosomes in the GnomAD database, including 591 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 0.075 (591 hom., cov: 32)
• Consequence: VPS41 ENST00000457055.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• Publications: 0 publications found

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]

VPS41 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 29

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive cerebellar ataxia-saccadic intrusion syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS41	ENST00000457055.1	c.-130+1441A>G		intron_variant	Intron 1 of 5	4		ENSP00000398584.1

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11426 AN: 152146 Hom.: 584 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0450

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0380

Gnomad OTH AF: 0.0837

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

GnomAD4 genome AF: 0.0753 AC: 11458 AN: 152264 Hom.: 591 Cov.: 32 AF XY: 0.0756 AC XY: 5627 AN XY: 74450

African (AFR) AF: 0.138 AC: 5716 AN: 41530

American (AMR) AF: 0.102 AC: 1556 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0450 AC: 156 AN: 3470

East Asian (EAS) AF: 0.0963 AC: 499 AN: 5184

South Asian (SAS) AF: 0.0633 AC: 305 AN: 4822

European-Finnish (FIN) AF: 0.0340 AC: 361 AN: 10618

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0380 AC: 2584 AN: 68024

Other (OTH) AF: 0.0837 AC: 177 AN: 2114

Alfa AF: 0.0510 Hom.: 512

Bravo AF: 0.0860

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs17171485; hg19: chr7-38970437;