rs2241270

Variant names:

• chr9-129752610-C-T
• rs2241270
• NM_004878.5:c.126+277G>A

Variant summary

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

The NM_004878.5(PTGES):​c.126+277G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,286 control chromosomes in the GnomAD database, including 2,651 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 (2651 hom., cov: 33)
• Consequence: PTGES NM_004878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453
• Publications: 7 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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGES	NM_004878.5	c.126+277G>A		intron_variant	Intron 1 of 2	ENST00000340607.5	NP_004869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGES	ENST00000340607.5	c.126+277G>A		intron_variant	Intron 1 of 2	1	NM_004878.5	ENSP00000342385.4
PTGES	ENST00000481476.1	n.133+277G>A		intron_variant	Intron 1 of 3	1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25628 AN: 152168 Hom.: 2635 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.169 AC: 25674 AN: 152286 Hom.: 2651 Cov.: 33 AF XY: 0.165 AC XY: 12318 AN XY: 74476

African (AFR) AF: 0.287 AC: 11898 AN: 41528

American (AMR) AF: 0.109 AC: 1667 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 418 AN: 3470

East Asian (EAS) AF: 0.176 AC: 912 AN: 5186

South Asian (SAS) AF: 0.153 AC: 740 AN: 4832

European-Finnish (FIN) AF: 0.0671 AC: 713 AN: 10624

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8876 AN: 68028

Other (OTH) AF: 0.166 AC: 351 AN: 2110

Alfa AF: 0.144 Hom.: 1254

Bravo AF: 0.176

Asia WGS AF: 0.202 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	10
DANN	Benign	0.94
PhyloP100		0.45
PromoterAI		0.074	Neutral
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: rs2241270; hg19: chr9-132514889;