rs3745459

Positions:

• chr19-14473505-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000955.3(PTGER1):​c.816C>T​(p.Ala272Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,579,088 control chromosomes in the GnomAD database, including 404 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 0.017 (42 hom., cov: 32)
  • Exomes 𝑓: 0.017 (362 hom.)
• Consequence: PTGER1 NM_000955.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

Genes affected

PTGER1 (HGNC:9593): (prostaglandin E receptor 1) 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). Through a phosphatidylinositol-calcium second messenger system, G-Q proteins mediate this receptor's activity. Knockout studies in mice suggested a role of this receptor in mediating algesia and in regulation of blood pressure. Studies in mice also suggested that this gene may mediate adrenocorticotropic hormone response to bacterial endotoxin. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=0.061 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGER1	NM_000955.3	c.816C>T	p.Ala272Ala	synonymous_variant	2/3	ENST00000292513.4	NP_000946.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGER1	ENST00000292513.4	c.816C>T	p.Ala272Ala	synonymous_variant	2/3	1	NM_000955.3	ENSP00000292513.3

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2643 AN: 152190 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.00678

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.0793

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.0320

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0248

GnomAD3 exomes AF: 0.0223 AC: 4030 AN: 180888 Hom.: 82 AF XY: 0.0212 AC XY: 2108 AN XY: 99648

Gnomad AFR exome AF: 0.00925

Gnomad AMR exome AF: 0.0247

Gnomad ASJ exome AF: 0.00948

Gnomad EAS exome AF: 0.0785

Gnomad SAS exome AF: 0.0114

Gnomad FIN exome AF: 0.0356

Gnomad NFE exome AF: 0.0158

Gnomad OTH exome AF: 0.0218

GnomAD4 exome AF: 0.0169 AC: 24081 AN: 1426780 Hom.: 362 Cov.: 32 AF XY: 0.0166 AC XY: 11716 AN XY: 707796

Gnomad4 AFR exome AF: 0.00708

Gnomad4 AMR exome AF: 0.0267

Gnomad4 ASJ exome AF: 0.00867

Gnomad4 EAS exome AF: 0.0738

Gnomad4 SAS exome AF: 0.0107

Gnomad4 FIN exome AF: 0.0322

Gnomad4 NFE exome AF: 0.0148

Gnomad4 OTH exome AF: 0.0195

GnomAD4 genome AF: 0.0174 AC: 2645 AN: 152308 Hom.: 42 Cov.: 32 AF XY: 0.0186 AC XY: 1386 AN XY: 74472

Gnomad4 AFR AF: 0.00681

Gnomad4 AMR AF: 0.0297

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.0794

Gnomad4 SAS AF: 0.0128

Gnomad4 FIN AF: 0.0320

Gnomad4 NFE AF: 0.0142

Gnomad4 OTH AF: 0.0250

Alfa AF: 0.0138 Hom.: 4

Bravo AF: 0.0179

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs3745459; hg19: chr19-14584317; COSMIC: COSV52874736; COSMIC: COSV52874736;