rs6458238

Positions:

• chr6-41749967-G-A
• chr6-41749967-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+3931C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 151,958 control chromosomes in the GnomAD database, including 2,960 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 0.15 (2960 hom., cov: 32)
• Consequence: PGC ENST00000415707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 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+3931C>T		intron_variant		5		ENSP00000399429.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22346 AN: 151840 Hom.: 2953 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.0867

Gnomad ASJ AF: 0.0802

Gnomad EAS AF: 0.0721

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0688

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.147 AC: 22381 AN: 151958 Hom.: 2960 Cov.: 32 AF XY: 0.142 AC XY: 10571 AN XY: 74270

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.0867

Gnomad4 ASJ AF: 0.0802

Gnomad4 EAS AF: 0.0726

Gnomad4 SAS AF: 0.0546

Gnomad4 FIN AF: 0.0248

Gnomad4 NFE AF: 0.0688

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0838 Hom.: 1021

Bravo AF: 0.164

Asia WGS AF: 0.0880 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6458238; hg19: chr6-41717705;