17-59772890-C-T

Variant names:

• chr17-59772890-C-T
• rs11650106
• NM_030938.5:c.583-864C>T

Variant summary

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

The NM_030938.5(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 NM_030938.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030938.5. 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
	VMP1	NM_030938.5	MANE Select	c.583-864C>T		intron	N/A	NP_112200.2
	VMP1	NM_001329395.2		c.583-864C>T		intron	N/A	NP_001316324.1
	VMP1	NM_001329394.2		c.583-864C>T		intron	N/A	NP_001316323.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VMP1	ENST00000262291.9	TSL:1 MANE Select	c.583-864C>T		intron	N/A	ENSP00000262291.3
	VMP1	ENST00000591877.2	TSL:3	c.583-864C>T		intron	N/A	ENSP00000467350.2
	VMP1	ENST00000891501.1		c.583-864C>T		intron	N/A	ENSP00000561560.1

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

African (AFR) AF: 0.180 AC: 7216 AN: 40176

American (AMR) AF: 0.451 AC: 6723 AN: 14920

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1778 AN: 3460

East Asian (EAS) AF: 0.408 AC: 2087 AN: 5120

South Asian (SAS) AF: 0.443 AC: 2114 AN: 4774

European-Finnish (FIN) AF: 0.491 AC: 4797 AN: 9778

Middle Eastern (MID) AF: 0.344 AC: 97 AN: 282

European-Non Finnish (NFE) AF: 0.533 AC: 36047 AN: 67688

Other (OTH) AF: 0.405 AC: 836 AN: 2066

Alfa AF: 0.493 Hom.: 46531

Bravo AF: 0.404

Asia WGS AF: 0.369 AC: 1280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.26
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11650106; hg19: chr17-57850251;