rs9471643

Positions:

• chr6-41751177-G-C

Variant summary

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

The ENST00000415707.1(PGC):​c.71+2721C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,062 control chromosomes in the GnomAD database, including 2,799 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 (2799 hom., cov: 33)
• Consequence: PGC ENST00000415707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGC	ENST00000415707.1	c.71+2721C>G		intron_variant		5		ENSP00000399429

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28660 AN: 151944 Hom.: 2800 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.189 AC: 28678 AN: 152062 Hom.: 2799 Cov.: 33 AF XY: 0.192 AC XY: 14299 AN XY: 74326

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.182

Alfa AF: 0.196 Hom.: 387

Bravo AF: 0.184

Asia WGS AF: 0.243 AC: 847 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	1.4
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9471643; hg19: chr6-41718915;