Variant 5-40691791-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000958.3(PTGER4):c.880G>A(p.Val294Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,613,004 control chromosomes in the GnomAD database, including 513 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 30 hom., cov: 33)

Exomes 𝑓: 0.024 ( 483 hom. )

Consequence

PTGER4
NM_000958.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.124

Variant links:

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]

PTGER4 links:

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

TTC33 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074923635).

BP6

Variant 5-40691791-G-A is Benign according to our data. Variant chr5-40691791-G-A is described in ClinVar as [Benign]. Clinvar id is 218477.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-40691791-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.017 (2583/152278) while in subpopulation NFE AF= 0.0261 (1778/68012). AF 95% confidence interval is 0.0251. There are 30 homozygotes in gnomad4. There are 1268 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2583 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGER4	NM_000958.3 linkuse as main transcript	c.880G>A	p.Val294Ile	missense_variant	3/3	ENST00000302472.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGER4	ENST00000302472.4 linkuse as main transcript	c.880G>A	p.Val294Ile	missense_variant	3/3	1	NM_000958.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2580

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00526

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.0233

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0261

Gnomad OTH

AF:

0.0154

GnomAD3 exomes

AF:

0.0167

AC:

4165

AN:

249968

Hom.:

AF XY:

0.0167

AC XY:

2256

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.00419

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.0129

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00725

Gnomad FIN exome

AF:

0.0251

Gnomad NFE exome

AF:

0.0242

Gnomad OTH exome

AF:

0.0202

GnomAD4 exome

AF:

0.0236

AC:

34453

AN:

1460726

Hom.:

483

Cov.:

AF XY:

0.0230

AC XY:

16747

AN XY:

726700

show subpopulations

Gnomad4 AFR exome

AF:

0.00506

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.0154

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00719

Gnomad4 FIN exome

AF:

0.0245

Gnomad4 NFE exome

AF:

0.0270

Gnomad4 OTH exome

AF:

0.0232

GnomAD4 genome

AF:

0.0170

AC:

2583

AN:

152278

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1268

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00529

Gnomad4 AMR

AF:

0.0137

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00662

Gnomad4 FIN

AF:

0.0233

Gnomad4 NFE

AF:

0.0261

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.0230

Hom.:

Bravo

AF:

0.0158

TwinsUK

AF:

0.0251

AC:

ALSPAC

AF:

0.0272

AC:

105

ESP6500AA

AF:

0.00567

AC:

ESP6500EA

AF:

0.0264

AC:

227

ExAC

AF:

0.0166

AC:

2019

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0249

EpiControl

AF:

0.0245

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Apr 17, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.8

DANN

Benign

0.72

DEOGEN2

Benign

0.11

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0075

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.10

REVEL

Benign

0.12

Sift

Benign

0.70

Sift4G

Benign

0.40

Polyphen

0.0020

Vest4

0.021

MPC

1.0

ClinPred

0.0016

GERP RS

-7.0

Varity_R

0.019

gMVP

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over