rs4837404

Variant names:

• chr9-129743380-G-A
• rs4837404
• NM_004878.5:c.210-3520C>T

Variant summary

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

The NM_004878.5(PTGES):​c.210-3520C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,168 control chromosomes in the GnomAD database, including 42,004 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 0.73 (42004 hom., cov: 32)
• Consequence: PTGES NM_004878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 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.210-3520C>T		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.210-3520C>T		intron	N/A	ENSP00000342385.4
	PTGES	ENST00000481476.1	TSL:1	n.339-3520C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111148 AN: 152050 Hom.: 41953 Cov.: 32

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.731 AC: 111255 AN: 152168 Hom.: 42004 Cov.: 32 AF XY: 0.731 AC XY: 54388 AN XY: 74378

African (AFR) AF: 0.936 AC: 38902 AN: 41572

American (AMR) AF: 0.705 AC: 10759 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2262 AN: 3470

East Asian (EAS) AF: 0.648 AC: 3349 AN: 5172

South Asian (SAS) AF: 0.710 AC: 3423 AN: 4824

European-Finnish (FIN) AF: 0.667 AC: 7064 AN: 10586

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43371 AN: 67970

Other (OTH) AF: 0.734 AC: 1548 AN: 2110

Alfa AF: 0.666 Hom.: 52039

Bravo AF: 0.744

Asia WGS AF: 0.710 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.56
PhyloP100		-0.98
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: rs4837404; hg19: chr9-132505659;