NM_004878.5:c.180G>A

Variant names:

• chr9-129748684-C-T
• rs142287855
• NM_004878.5:c.180G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004878.5(PTGES):​c.180G>A​(p.Arg60Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 1,583,684 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (29 hom.)
• Consequence: PTGES NM_004878.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.251
• Publications: 1 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-129748684-C-T is Benign according to our data. Variant chr9-129748684-C-T is described in ClinVar as Benign. ClinVar VariationId is 710270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.251 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES	NM_004878.5	MANE Select	c.180G>A	p.Arg60Arg	synonymous	Exon 2 of 3	NP_004869.1	O14684

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES	ENST00000340607.5	TSL:1 MANE Select	c.180G>A	p.Arg60Arg	synonymous	Exon 2 of 3	ENSP00000342385.4	O14684
	PTGES	ENST00000481476.1	TSL:1	n.309G>A		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.00466 AC: 709 AN: 152168 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00629

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00487 AC: 1063 AN: 218486 AF XY: 0.00490

Gnomad AFR exome AF: 0.00101

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00254

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0122

Gnomad NFE exome AF: 0.00710

Gnomad OTH exome AF: 0.00348

GnomAD4 exome AF: 0.00573 AC: 8195 AN: 1431398 Hom.: 29 Cov.: 30 AF XY: 0.00564 AC XY: 4017 AN XY: 712212

African (AFR) AF: 0.000904 AC: 28 AN: 30960

American (AMR) AF: 0.00135 AC: 51 AN: 37748

Ashkenazi Jewish (ASJ) AF: 0.00218 AC: 55 AN: 25194

East Asian (EAS) AF: 0.00 AC: 0 AN: 36732

South Asian (SAS) AF: 0.000134 AC: 11 AN: 81840

European-Finnish (FIN) AF: 0.0108 AC: 572 AN: 53138

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5688

European-Non Finnish (NFE) AF: 0.00654 AC: 7199 AN: 1100974

Other (OTH) AF: 0.00467 AC: 276 AN: 59124

GnomAD4 genome AF: 0.00466 AC: 709 AN: 152286 Hom.: 4 Cov.: 32 AF XY: 0.00498 AC XY: 371 AN XY: 74470

African (AFR) AF: 0.000963 AC: 40 AN: 41550

American (AMR) AF: 0.00418 AC: 64 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0150 AC: 159 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00629 AC: 428 AN: 68024

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00466 Hom.: 0

Bravo AF: 0.00381

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.8
DANN	Benign	0.40
PhyloP100		0.25
Mutation Taster		=99/1	polymorphism

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: rs142287855; hg19: chr9-132510963;