7-38727164-A-C

Position:

• chr7-38727164-A-C

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.2405-176T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 471,964 control chromosomes in the GnomAD database, including 29,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7787 hom., cov: 33)
  • Exomes 𝑓: 0.35 (21990 hom.)
• Consequence: VPS41 NM_014396.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.492

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=-0.9).
• BP6: Variant 7-38727164-A-C is Benign according to our data. Variant chr7-38727164-A-C is described in ClinVar as [Benign]. Clinvar id is 1282659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS41	NM_014396.4	c.2405-176T>G		intron_variant		ENST00000310301.9
VPS41	NM_080631.4	c.2330-176T>G		intron_variant
VPS41	XM_017011988.2	c.1250-176T>G		intron_variant
VPS41	XR_007060008.1	n.2516-176T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS41	ENST00000310301.9	c.2405-176T>G		intron_variant		1	NM_014396.4	P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43886 AN: 152086 Hom.: 7787 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.350 AC: 112025 AN: 319760 Hom.: 21990 Cov.: 5 AF XY: 0.346 AC XY: 57212 AN XY: 165280

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.0687

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.436

Gnomad4 NFE exome AF: 0.404

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.288 AC: 43881 AN: 152204 Hom.: 7787 Cov.: 33 AF XY: 0.285 AC XY: 21224 AN XY: 74406

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.275

Alfa AF: 0.364 Hom.: 5167

Bravo AF: 0.267

Asia WGS AF: 0.117 AC: 410 AN: 3478

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.55

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: rs7803132; hg19: chr7-38766764;