rs6912200

Variant names:

• chr6-41750170-C-T
• rs6912200
• ENST00000415707.1:c.71+3728G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 = 0.683 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.71+3728G>A		intron_variant	Intron 1 of 2	5		ENSP00000399429.1

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

African (AFR) AF: 0.288 AC: 11935 AN: 41458

American (AMR) AF: 0.442 AC: 6764 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2052 AN: 3468

East Asian (EAS) AF: 0.492 AC: 2539 AN: 5162

South Asian (SAS) AF: 0.480 AC: 2312 AN: 4820

European-Finnish (FIN) AF: 0.737 AC: 7792 AN: 10572

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46776 AN: 67978

Other (OTH) AF: 0.562 AC: 1184 AN: 2108

Alfa AF: 0.636 Hom.: 76469

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
PhyloP100		0.25

Splicing

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

Other links and lift over

dbSNP: rs6912200; hg19: chr6-41717908;