19-14473261-C-T

Position:

• chr19-14473261-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000955.3(PTGER1):​c.942+118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 1,470,470 control chromosomes in the GnomAD database, including 4,765 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 0.10 (2646 hom., cov: 32)
  • Exomes 𝑓: 0.011 (2119 hom.)
• Consequence: PTGER1 NM_000955.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGER1	NM_000955.3	c.942+118G>A		intron_variant		ENST00000292513.4	NP_000946.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGER1	ENST00000292513.4	c.942+118G>A		intron_variant		1	NM_000955.3	ENSP00000292513	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15603 AN: 151946 Hom.: 2632 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0422

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00200

Gnomad OTH AF: 0.0798

GnomAD4 exome AF: 0.0109 AC: 14334 AN: 1318408 Hom.: 2119 AF XY: 0.00964 AC XY: 6226 AN XY: 645908

Gnomad4 AFR exome AF: 0.369

Gnomad4 AMR exome AF: 0.0261

Gnomad4 ASJ exome AF: 0.00981

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.000380

Gnomad4 NFE exome AF: 0.00118

Gnomad4 OTH exome AF: 0.0262

GnomAD4 genome AF: 0.103 AC: 15646 AN: 152062 Hom.: 2646 Cov.: 32 AF XY: 0.0997 AC XY: 7414 AN XY: 74364

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.0420

Gnomad4 ASJ AF: 0.00720

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00199

Gnomad4 OTH AF: 0.0790

Alfa AF: 0.0238 Hom.: 72

Bravo AF: 0.118

Asia WGS AF: 0.0230 AC: 80 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	2.5
DANN	Benign	0.71

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: rs10421765; hg19: chr19-14584073; COSMIC: COSV52876479; COSMIC: COSV52876479;