Variant rs4711690 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001166424.2(PGC):c.723G>C(p.Gln241His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,525,826 control chromosomes in the GnomAD database, including 21,628 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3220 hom., cov: 32)

Exomes 𝑓: 0.16 ( 18408 hom. )

Consequence

PGC
NM_001166424.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.714

Variant links:

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]

PGC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005326152).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGC	NM_002630.4 link	c.648-590G>C		intron_variant	Intron 5 of 8	ENST00000373025.7	NP_002621.1	P20142-1
PGC	NM_001166424.2 link	c.723G>C	p.Gln241His	missense_variant	Exon 7 of 7		NP_001159896.1	P20142-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PGC	ENST00000373025.7 link	c.648-590G>C		intron_variant	Intron 5 of 8	1	NM_002630.4	ENSP00000362116.3	P20142-1
PGC	ENST00000425343.6 link	c.723G>C	p.Gln241His	missense_variant	Exon 7 of 7	2		ENSP00000405094.2	P20142-2
PGC	ENST00000356667.8 link	c.411-590G>C		intron_variant	Intron 3 of 3	5		ENSP00000349094.4	Q4VXA6

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29668

AN:

151978

Hom.:

3217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.196

GnomAD3 exomes

AF:

0.192

AC:

26057

AN:

135412

Hom.:

2788

AF XY:

0.185

AC XY:

13405

AN XY:

72304

show subpopulations

Gnomad AFR exome

AF:

0.258

Gnomad AMR exome

AF:

0.291

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.231

Gnomad SAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.150

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.158

AC:

216833

AN:

1373730

Hom.:

18408

Cov.:

AF XY:

0.157

AC XY:

106027

AN XY:

676448

show subpopulations

Gnomad4 AFR exome

AF:

0.265

Gnomad4 AMR exome

AF:

0.291

Gnomad4 ASJ exome

AF:

0.274

Gnomad4 EAS exome

AF:

0.269

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.122

Gnomad4 NFE exome

AF:

0.145

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.195

AC:

29712

AN:

152096

Hom.:

3220

Cov.:

AF XY:

0.195

AC XY:

14519

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.260

Gnomad4 AMR

AF:

0.263

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.237

Gnomad4 SAS

AF:

0.140

Gnomad4 FIN

AF:

0.112

Gnomad4 NFE

AF:

0.152

Gnomad4 OTH

AF:

0.194

Alfa

AF:

0.187

Hom.:

541

Bravo

AF:

0.211

TwinsUK

AF:

0.141

AC:

521

ALSPAC

AF:

0.145

AC:

560

ExAC

AF:

0.145

AC:

3153

Asia WGS

AF:

0.202

AC:

703

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0053

MetaSVM

Benign

-0.98

PROVEAN

Benign

-0.47

REVEL

Benign

0.041

Sift

Uncertain

0.011

Sift4G

Uncertain

0.030

Vest4

0.011

MutPred

0.42

Loss of sheet (P = 0.0126);

ClinPred

0.0030

GERP RS

-2.5

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over