6-41751372-T-C

Variant names:

• chr6-41751372-T-C
• rs6941539
• ENST00000415707.1:c.71+2526A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000415707.1(PGC):​c.71+2526A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 152,270 control chromosomes in the GnomAD database, including 67,254 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 0.94 (67254 hom., cov: 32)
• Consequence: PGC ENST00000415707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000415707.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGC	ENST00000415707.1	TSL:5	c.71+2526A>G		intron	N/A	ENSP00000399429.1

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142458 AN: 152152 Hom.: 67196 Cov.: 32

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.992

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.934

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

GnomAD4 genome AF: 0.936 AC: 142568 AN: 152270 Hom.: 67254 Cov.: 32 AF XY: 0.931 AC XY: 69333 AN XY: 74454

African (AFR) AF: 0.945 AC: 39242 AN: 41542

American (AMR) AF: 0.750 AC: 11455 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 3288 AN: 3472

East Asian (EAS) AF: 0.838 AC: 4336 AN: 5172

South Asian (SAS) AF: 0.872 AC: 4211 AN: 4828

European-Finnish (FIN) AF: 0.992 AC: 10528 AN: 10618

Middle Eastern (MID) AF: 0.973 AC: 284 AN: 292

European-Non Finnish (NFE) AF: 0.976 AC: 66388 AN: 68042

Other (OTH) AF: 0.935 AC: 1975 AN: 2112

Alfa AF: 0.957 Hom.: 106236

Bravo AF: 0.918

Asia WGS AF: 0.842 AC: 2928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.9
DANN	Benign	0.87
PhyloP100		0.048

Splicing

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

Other links and lift over

dbSNP: rs6941539; hg19: chr6-41719110;