Genetic Variant NM_000955.3:c.816C>T (chr19-14473505-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0610

Publications

7 publications found

Variant links:

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]

PTGER1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PTGER1	NM_000955.3 link	c.816C>T	p.Ala272Ala	synonymous_variant	Exon 2 of 3	ENST00000292513.4	NP_000946.2	P34995

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGER1	ENST00000292513.4 link	c.816C>T	p.Ala272Ala	synonymous_variant	Exon 2 of 3	1	NM_000955.3	ENSP00000292513.3		P34995

Frequencies

GnomAD3 genomes

AF:

0.0174

AC:

2643

AN:

152190

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0223

AC:

4030

AN:

180888

AF XY:

0.0212

show subpopulations

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 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.:

AF XY:

0.0166

AC XY:

11716

AN XY:

707796

show subpopulations

African (AFR)

AF:

0.00708

AC:

231

AN:

32644

American (AMR)

AF:

0.0267

AC:

1074

AN:

40268

Ashkenazi Jewish (ASJ)

AF:

0.00867

AC:

222

AN:

25604

East Asian (EAS)

AF:

0.0738

AC:

2796

AN:

37888

South Asian (SAS)

AF:

0.0107

AC:

882

AN:

82506

European-Finnish (FIN)

AF:

0.0322

AC:

1429

AN:

44352

Middle Eastern (MID)

AF:

0.0112

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0148

AC:

16225

AN:

1098578

Other (OTH)

AF:

0.0195

AC:

1158

AN:

59242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1519

3039

4558

6078

7597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

668

1336

2004

2672

3340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0174

AC:

2645

AN:

152308

Hom.:

Cov.:

AF XY:

0.0186

AC XY:

1386

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00681

AC:

283

AN:

41574

American (AMR)

AF:

0.0297

AC:

454

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00979

AC:

AN:

3472

East Asian (EAS)

AF:

0.0794

AC:

411

AN:

5174

South Asian (SAS)

AF:

0.0128

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0320

AC:

340

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0142

AC:

965

AN:

68016

Other (OTH)

AF:

0.0250

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

131

262

394

525

656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0120

Hom.:

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

(source)

DANN

Benign

0.83

PhyloP100

0.061

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over