17-59772890-C-T

Position:

• chr17-59772890-C-T

Variant summary

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

The ENST00000262291.9(VMP1):​c.583-864C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 149,160 control chromosomes in the GnomAD database, including 14,635 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 0.42 (14635 hom., cov: 28)
• Consequence: VMP1 ENST00000262291.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VMP1	NM_030938.5	c.583-864C>T		intron_variant		ENST00000262291.9	NP_112200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VMP1	ENST00000262291.9	c.583-864C>T		intron_variant		1	NM_030938.5	ENSP00000262291	P1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 62103 AN: 149102 Hom.: 14635 Cov.: 28

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.416 AC: 62110 AN: 149160 Hom.: 14635 Cov.: 28 AF XY: 0.415 AC XY: 30160 AN XY: 72680

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.405

Alfa AF: 0.505 Hom.: 18904

Bravo AF: 0.404

Asia WGS AF: 0.369 AC: 1280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.26

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: rs11650106; hg19: chr17-57850251;