7-38742222-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014396.4(VPS41):c.2123-101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,155,590 control chromosomes in the GnomAD database, including 27,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4818 hom., cov: 32)
  • Exomes 𝑓: 0.20 (22419 hom.)
• Consequence: VPS41 NM_014396.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0980

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-38742222-C-T is Benign according to our data. Variant chr7-38742222-C-T is described in ClinVar as [Benign]. Clinvar id is 1230897.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS41	NM_014396.4	c.2123-101G>A		intron_variant		ENST00000310301.9
VPS41	NM_080631.4	c.2048-101G>A		intron_variant
VPS41	XM_017011988.2	c.968-101G>A		intron_variant
VPS41	XR_007060008.1	n.2140-101G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS41	ENST00000310301.9	c.2123-101G>A		intron_variant		1	NM_014396.4	P1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35521 AN: 151848 Hom.: 4815 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.195 AC: 196184 AN: 1003624 Hom.: 22419 AF XY: 0.201 AC XY: 100790 AN XY: 500752

Gnomad4 AFR exome AF: 0.345

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.233

Gnomad4 EAS exome AF: 0.421

Gnomad4 SAS exome AF: 0.396

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.234 AC: 35551 AN: 151966 Hom.: 4818 Cov.: 32 AF XY: 0.238 AC XY: 17689 AN XY: 74292

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.216

Alfa AF: 0.205 Hom.: 434

Bravo AF: 0.231

Asia WGS AF: 0.389 AC: 1347 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.3
Dann	Benign	0.27

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: rs17700392; hg19: chr7-38781822;