rs3789210

Positions:

• chr6-41743584-C-G
• chr6-41743584-C-T

Variant summary

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

The NM_002630.4(PGC):​c.329-195G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 152,260 control chromosomes in the GnomAD database, including 691 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 0.092 (691 hom., cov: 32)
• Consequence: PGC NM_002630.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGC	NM_002630.4	c.329-195G>C		intron_variant		ENST00000373025.7	NP_002621.1
PGC	NM_001166424.2	c.329-195G>C		intron_variant			NP_001159896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGC	ENST00000373025.7	c.329-195G>C		intron_variant		1	NM_002630.4	ENSP00000362116.3
PGC	ENST00000425343.6	c.329-195G>C		intron_variant		2		ENSP00000405094.2
PGC	ENST00000356667.8	c.210+1074G>C		intron_variant		5		ENSP00000349094.4

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13977 AN: 152142 Hom.: 691 Cov.: 32

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0645

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.0954

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0747

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

GnomAD4 genome AF: 0.0919 AC: 13988 AN: 152260 Hom.: 691 Cov.: 32 AF XY: 0.0946 AC XY: 7041 AN XY: 74444

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.0643

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.0953

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.0749

Alfa AF: 0.0424 Hom.: 51

Bravo AF: 0.0816

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3789210; hg19: chr6-41711322;