ENST00000457055.1:c.-130+1712G>A

Variant names:

• chr7-38930566-C-T
• rs859522
• ENST00000457055.1:c.-130+1712G>A

Variant summary

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

The ENST00000457055.1(VPS41):​c.-130+1712G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,214 control chromosomes in the GnomAD database, including 51,744 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 0.81 (51744 hom., cov: 33)
• Consequence: VPS41 ENST00000457055.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000457055.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS41	ENST00000457055.1	TSL:4	c.-130+1712G>A		intron	N/A	ENSP00000398584.1	C9J2U9

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123584 AN: 152096 Hom.: 51724 Cov.: 33

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.797

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

GnomAD4 genome AF: 0.812 AC: 123652 AN: 152214 Hom.: 51744 Cov.: 33 AF XY: 0.807 AC XY: 60068 AN XY: 74438

African (AFR) AF: 0.670 AC: 27793 AN: 41494

American (AMR) AF: 0.811 AC: 12399 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 3004 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1714 AN: 5166

South Asian (SAS) AF: 0.715 AC: 3447 AN: 4818

European-Finnish (FIN) AF: 0.923 AC: 9802 AN: 10614

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.923 AC: 62769 AN: 68034

Other (OTH) AF: 0.797 AC: 1684 AN: 2114

Alfa AF: 0.877 Hom.: 33662

Bravo AF: 0.793

Asia WGS AF: 0.527 AC: 1834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.36
PhyloP100		-0.29

Splicing

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

Other links and lift over

dbSNP: rs859522; hg19: chr7-38970166;