rs1292037

Variant names:

• chr17-59841547-T-C
• rs1292037
• NM_030938.5:c.*1636T>C

Variant summary

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

The NM_030938.5(VMP1):​c.*1636T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 207,612 control chromosomes in the GnomAD database, including 5,544 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 0.19 (3209 hom., cov: 32)
  • Exomes 𝑓: 0.26 (2335 hom.)
• Consequence: VMP1 NM_030938.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 25 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]

MIR21 (HGNC:31586): (microRNA 21) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 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.*1636T>C		3_prime_UTR	Exon 12 of 12	NP_112200.2
	VMP1	NM_001329395.2		c.*1636T>C		3_prime_UTR	Exon 13 of 13	NP_001316324.1	K7EPE7
	VMP1	NM_001329394.2		c.*1636T>C		3_prime_UTR	Exon 12 of 12	NP_001316323.1	Q96GC9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VMP1	ENST00000262291.9	TSL:1 MANE Select	c.*1636T>C		3_prime_UTR	Exon 12 of 12	ENSP00000262291.3	Q96GC9-1
	VMP1	ENST00000591877.2	TSL:3	c.*1636T>C		3_prime_UTR	Exon 13 of 13	ENSP00000467350.2	K7EPE7
	VMP1	ENST00000587259.6	TSL:4	c.*1636T>C		3_prime_UTR	Exon 13 of 13	ENSP00000465397.2	Q96GC9-1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28121 AN: 151942 Hom.: 3199 Cov.: 32

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.260 AC: 14456 AN: 55552 Hom.: 2335 Cov.: 0 AF XY: 0.280 AC XY: 8759 AN XY: 31278

African (AFR) AF: 0.0695 AC: 168 AN: 2416

American (AMR) AF: 0.155 AC: 811 AN: 5224

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 206 AN: 1116

East Asian (EAS) AF: 0.449 AC: 1961 AN: 4366

South Asian (SAS) AF: 0.423 AC: 4830 AN: 11418

European-Finnish (FIN) AF: 0.233 AC: 591 AN: 2540

Middle Eastern (MID) AF: 0.154 AC: 20 AN: 130

European-Non Finnish (NFE) AF: 0.205 AC: 5343 AN: 26060

Other (OTH) AF: 0.231 AC: 526 AN: 2282

GnomAD4 genome AF: 0.185 AC: 28137 AN: 152060 Hom.: 3209 Cov.: 32 AF XY: 0.189 AC XY: 14070 AN XY: 74338

African (AFR) AF: 0.0826 AC: 3428 AN: 41514

American (AMR) AF: 0.172 AC: 2624 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 688 AN: 3464

East Asian (EAS) AF: 0.438 AC: 2259 AN: 5160

South Asian (SAS) AF: 0.410 AC: 1975 AN: 4822

European-Finnish (FIN) AF: 0.211 AC: 2228 AN: 10558

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.210 AC: 14262 AN: 67976

Other (OTH) AF: 0.202 AC: 425 AN: 2106

Alfa AF: 0.186 Hom.: 460

Bravo AF: 0.171

Asia WGS AF: 0.420 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.80
PhyloP100		0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1292037; hg19: chr17-57918908;