NM_004878.5:c.209+3024A>G

Variant names:

• chr9-129745631-T-C
• rs10739757
• NM_004878.5:c.209+3024A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004878.5. 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
	PTGES	NM_004878.5	MANE Select	c.209+3024A>G		intron	N/A	NP_004869.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES	ENST00000340607.5	TSL:1 MANE Select	c.209+3024A>G		intron	N/A	ENSP00000342385.4
	PTGES	ENST00000481476.1	TSL:1	n.338+3024A>G		intron	N/A

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

African (AFR) AF: 0.293 AC: 12155 AN: 41484

American (AMR) AF: 0.140 AC: 2146 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3472

East Asian (EAS) AF: 0.213 AC: 1104 AN: 5172

South Asian (SAS) AF: 0.196 AC: 945 AN: 4816

European-Finnish (FIN) AF: 0.0633 AC: 671 AN: 10604

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7539 AN: 68002

Other (OTH) AF: 0.160 AC: 338 AN: 2108

Alfa AF: 0.133 Hom.: 6396

Bravo AF: 0.180

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.41
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10739757; hg19: chr9-132507910;