rs10739757

chr9-129745631-T-C

Variant summary

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

The NM_004878.5(PTGES):c.209+3024A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,144 control chromosomes in the GnomAD database, including 2,674 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 0.17 (2674 hom., cov: 31)
• Consequence: PTGES NM_004878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

Genes affected

PTGES (HGNC:9599): (prostaglandin E synthase) The protein encoded by this gene is a glutathione-dependent prostaglandin E synthase. The expression of this gene has been shown to be induced by proinflammatory cytokine interleukin 1 beta (IL1B). Its expression can also be induced by tumor suppressor protein TP53, and may be involved in TP53 induced apoptosis. Knockout studies in mice suggest that this gene may contribute to the pathogenesis of collagen-induced arthritis and mediate acute pain during inflammatory responses. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGES	NM_004878.5	c.209+3024A>G		intron_variant		ENST00000340607.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGES	ENST00000340607.5	c.209+3024A>G		intron_variant		1	NM_004878.5	P1
PTGES	ENST00000481476.1	n.338+3024A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25455 AN: 152026 Hom.: 2661 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0633

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.168 AC: 25500 AN: 152144 Hom.: 2674 Cov.: 31 AF XY: 0.166 AC XY: 12310 AN XY: 74380

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.0633

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.160

Alfa AF: 0.125 Hom.: 2635

Bravo AF: 0.180

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.4
Dann	Benign	0.41

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

Other links and lift over

dbSNP: rs10739757; hg19: chr9-132507910;