17-59755030-T-G

Position:

• chr17-59755030-T-G

Variant summary

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

The NM_030938.5(VMP1):​c.415-9941T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 142,236 control chromosomes in the GnomAD database, including 14,323 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 0.43 (14323 hom., cov: 22)
• Consequence: VMP1 NM_030938.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

Genes affected

VMP1 (HGNC:29559): (vacuole membrane protein 1) This gene encodes a transmembrane protein that plays a key regulatory role in the process of autophagy. The ectopic overexpression of the encoded protein in cultured cells triggers autophagy even under nutrient-rich conditions. This gene is overexpressed in pancreatitis affected acinar cells where the encoded protein mediates sequestration and degradation of potentially deleterious activated zymogen granules in a process termed, zymophagy. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VMP1	NM_030938.5	c.415-9941T>G		intron_variant		ENST00000262291.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VMP1	ENST00000262291.9	c.415-9941T>G		intron_variant		1	NM_030938.5	P1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 60739 AN: 142138 Hom.: 14324 Cov.: 22

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.374

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.427 AC: 60744 AN: 142236 Hom.: 14323 Cov.: 22 AF XY: 0.426 AC XY: 29282 AN XY: 68782

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.421

Alfa AF: 0.478 Hom.: 7481

Bravo AF: 0.405

Asia WGS AF: 0.370 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.4
DANN	Benign	0.61

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: rs2777899; hg19: chr17-57832391;