rs2228058

Variant names:

• chr5-40681152-C-T
• rs2228058
• NM_000958.3:c.159C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000958.3(PTGER4):​c.159C>T​(p.Thr53Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 1,614,044 control chromosomes in the GnomAD database, including 4,537 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 0.083 (578 hom., cov: 32)
  • Exomes 𝑓: 0.070 (3959 hom.)
• Consequence: PTGER4 NM_000958.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604
• Publications: 16 publications found

Genes affected

PTGER4 (HGNC:9596): (prostaglandin E receptor 4) The protein encoded by this gene is a member of the G-protein coupled receptor family. This protein is one of four receptors identified for prostaglandin E2 (PGE2). This receptor can activate T-cell factor signaling. It has been shown to mediate PGE2 induced expression of early growth response 1 (EGR1), regulate the level and stability of cyclooxygenase-2 mRNA, and lead to the phosphorylation of glycogen synthase kinase-3. Knockout studies in mice suggest that this receptor may be involved in the neonatal adaptation of circulatory system, osteoporosis, as well as initiation of skin immune responses. [provided by RefSeq, Jul 2008]

TTC33 (HGNC:29959): (tetratricopeptide repeat domain 33)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.604 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000958.3. 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
	PTGER4	NM_000958.3	MANE Select	c.159C>T	p.Thr53Thr	synonymous	Exon 2 of 3	NP_000949.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGER4	ENST00000302472.4	TSL:1 MANE Select	c.159C>T	p.Thr53Thr	synonymous	Exon 2 of 3	ENSP00000302846.3
	PTGER4	ENST00000514343.1	TSL:1	n.751C>T		non_coding_transcript_exon	Exon 2 of 2
	PTGER4	ENST00000963428.1		c.159C>T	p.Thr53Thr	synonymous	Exon 2 of 3	ENSP00000633487.1

Frequencies

GnomAD3 genomes AF: 0.0829 AC: 12608 AN: 152058 Hom.: 577 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0563

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0367

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.0651

GnomAD2 exomes AF: 0.0653 AC: 16408 AN: 251398 AF XY: 0.0646

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0360

Gnomad ASJ exome AF: 0.0699

Gnomad EAS exome AF: 0.000653

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.0734

Gnomad OTH exome AF: 0.0693

GnomAD4 exome AF: 0.0701 AC: 102531 AN: 1461868 Hom.: 3959 Cov.: 32 AF XY: 0.0696 AC XY: 50633 AN XY: 727232

African (AFR) AF: 0.107 AC: 3584 AN: 33480

American (AMR) AF: 0.0370 AC: 1654 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0765 AC: 2000 AN: 26136

East Asian (EAS) AF: 0.000630 AC: 25 AN: 39700

South Asian (SAS) AF: 0.0419 AC: 3613 AN: 86258

European-Finnish (FIN) AF: 0.123 AC: 6569 AN: 53398

Middle Eastern (MID) AF: 0.0648 AC: 374 AN: 5768

European-Non Finnish (NFE) AF: 0.0724 AC: 80555 AN: 1112008

Other (OTH) AF: 0.0688 AC: 4157 AN: 60396

GnomAD4 genome AF: 0.0829 AC: 12621 AN: 152176 Hom.: 578 Cov.: 32 AF XY: 0.0837 AC XY: 6231 AN XY: 74408

African (AFR) AF: 0.111 AC: 4611 AN: 41504

American (AMR) AF: 0.0562 AC: 859 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0787 AC: 273 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5182

South Asian (SAS) AF: 0.0367 AC: 177 AN: 4820

European-Finnish (FIN) AF: 0.136 AC: 1436 AN: 10586

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0749 AC: 5095 AN: 68008

Other (OTH) AF: 0.0644 AC: 136 AN: 2112

Alfa AF: 0.0738 Hom.: 788

Bravo AF: 0.0770

Asia WGS AF: 0.0270 AC: 92 AN: 3478

EpiCase AF: 0.0709

EpiControl AF: 0.0650

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.95
PhyloP100		0.60
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: rs2228058; hg19: chr5-40681254; COSMIC: COSV56722677; COSMIC: COSV56722677;