rs6912200

chr6-41750170-C-T

Variant summary

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

The ENST00000415707.1(PGC):c.71+3728G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,058 control chromosomes in the GnomAD database, including 24,547 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 0.54 (24547 hom., cov: 32)
• Consequence: PGC ENST00000415707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGC	ENST00000415707.1	c.71+3728G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82029 AN: 151940 Hom.: 24538 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.540 AC: 82055 AN: 152058 Hom.: 24547 Cov.: 32 AF XY: 0.537 AC XY: 39952 AN XY: 74344

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.562

Alfa AF: 0.647 Hom.: 52816

Bravo AF: 0.502

Asia WGS AF: 0.462 AC: 1601 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	5.5
Dann	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6912200; hg19: chr6-41717908;