rs2040017

Variant names:

• chr6-41748259-C-T
• rs2040017
• ENST00000415707.1:c.72-3451G>A

Variant summary

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

The ENST00000415707.1(PGC):​c.72-3451G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,146 control chromosomes in the GnomAD database, including 53,412 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 0.83 (53412 hom., cov: 32)
• Consequence: PGC ENST00000415707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 3 publications found

Genes affected

PGC (HGNC:8890): (progastricsin) This gene encodes an aspartic proteinase that belongs to the peptidase family A1. The encoded protein is a digestive enzyme that is produced in the stomach and constitutes a major component of the gastric mucosa. This protein is also secreted into the serum. This protein is synthesized as an inactive zymogen that includes a highly basic prosegment. This enzyme is converted into its active mature form at low pH by sequential cleavage of the prosegment that is carried out by the enzyme itself. Polymorphisms in this gene are associated with susceptibility to gastric cancers. Serum levels of this enzyme are used as a biomarker for certain gastric diseases including Helicobacter pylori related gastritis. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 1. [provided by RefSeq, Oct 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGC	ENST00000415707.1	c.72-3451G>A		intron_variant	Intron 1 of 2	5		ENSP00000399429.1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126434 AN: 152028 Hom.: 53368 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.832 AC: 126529 AN: 152146 Hom.: 53412 Cov.: 32 AF XY: 0.830 AC XY: 61760 AN XY: 74376

African (AFR) AF: 0.726 AC: 30108 AN: 41464

American (AMR) AF: 0.704 AC: 10761 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3046 AN: 3470

East Asian (EAS) AF: 0.761 AC: 3932 AN: 5168

South Asian (SAS) AF: 0.821 AC: 3949 AN: 4812

European-Finnish (FIN) AF: 0.967 AC: 10260 AN: 10614

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61739 AN: 68014

Other (OTH) AF: 0.833 AC: 1760 AN: 2112

Alfa AF: 0.876 Hom.: 91975

Bravo AF: 0.806

Asia WGS AF: 0.763 AC: 2653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.033
DANN	Benign	0.60
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs2040017; hg19: chr6-41715997;