1-70952977-C-T

Variant names:

• chr1-70952977-C-T
• rs369540225
• ENST00000356595.8:c.1187G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_198718.2(PTGER3):​c.1187G>A​(p.Arg396Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: PTGER3 NM_198718.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0170
• Publications: 0 publications found

Genes affected

PTGER3 (HGNC:9595): (prostaglandin E receptor 3) 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 may have many biological functions, which involve digestion, nervous system, kidney reabsorption, and uterine contraction activities. Studies of the mouse counterpart suggest that this receptor may also mediate adrenocorticotropic hormone response as well as fever generation in response to exogenous and endogenous stimuli. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043345362).
• BP6: Variant 1-70952977-C-T is Benign according to our data. Variant chr1-70952977-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3427505.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198718.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGER3	NM_198718.2		c.1187G>A	p.Arg396Lys	missense	Exon 4 of 4	NP_942011.1	P43115-5
	PTGER3	NM_001126044.2		c.*106G>A		3_prime_UTR	Exon 5 of 5	NP_001119516.1	P43115-1
	PTGER3	NM_198714.2		c.*23+786G>A		intron	N/A	NP_942007.1	P43115-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGER3	ENST00000356595.8	TSL:1	c.1187G>A	p.Arg396Lys	missense	Exon 4 of 4	ENSP00000349003.4	P43115-5
	PTGER3	ENST00000370931.7	TSL:1	c.*23+786G>A		intron	N/A	ENSP00000359969.3	P43115-1
	PTGER3	ENST00000460330.5	TSL:1	c.1104+786G>A		intron	N/A	ENSP00000418073.1	P43115-4

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000320 AC: 8 AN: 249806 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000713

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000349 AC: 51 AN: 1461020 Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22 AN XY: 726848

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000450 AC: 50 AN: 1111424

Other (OTH) AF: 0.0000166 AC: 1 AN: 60350

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74424

African (AFR) AF: 0.0000241 AC: 1 AN: 41542

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000959 Hom.: 0

Bravo AF: 0.0000642

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000274

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.74
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00051	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.91	T
PhyloP100		-0.017
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.054
Sift	Benign	0.70	T
Sift4G	Benign	1.0	T
Vest4		0.034
MVP		0.10
MPC		0.72
ClinPred		0.017	T
GERP RS		-2.0
gMVP		0.16
Mutation Taster		=98/2	polymorphism

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: rs369540225; hg19: chr1-71418660; COSMIC: COSV100656572; COSMIC: COSV100656572;