chr1-71047531-C-T

Variant names:

• chr1-71047531-C-T
• rs200764199
• NM_198719.2:c.47G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198719.2(PTGER3):​c.47G>A​(p.Arg16His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000309 in 1,587,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: PTGER3 NM_198719.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.718
• Publications: 1 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]

ZRANB2-AS1 (HGNC:43594): (ZRANB2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.02133581).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198719.2. 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_198719.2	MANE Select	c.47G>A	p.Arg16His	missense	Exon 1 of 4	NP_942012.1	P43115-1
	PTGER3	NM_198718.2		c.47G>A	p.Arg16His	missense	Exon 1 of 4	NP_942011.1	P43115-5
	PTGER3	NM_001126044.2		c.47G>A	p.Arg16His	missense	Exon 1 of 5	NP_001119516.1	P43115-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGER3	ENST00000306666.10	TSL:1 MANE Select	c.47G>A	p.Arg16His	missense	Exon 1 of 4	ENSP00000302313.5	P43115-1
	PTGER3	ENST00000356595.8	TSL:1	c.47G>A	p.Arg16His	missense	Exon 1 of 4	ENSP00000349003.4	P43115-5
	PTGER3	ENST00000370931.7	TSL:1	c.47G>A	p.Arg16His	missense	Exon 1 of 5	ENSP00000359969.3	P43115-1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000113 AC: 23 AN: 204064 AF XY: 0.0000629

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000342

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00145

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000272 AC: 39 AN: 1435592 Hom.: 0 Cov.: 31 AF XY: 0.0000267 AC XY: 19 AN XY: 710874

African (AFR) AF: 0.00 AC: 0 AN: 33250

American (AMR) AF: 0.0000247 AC: 1 AN: 40432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25490

East Asian (EAS) AF: 0.000957 AC: 37 AN: 38674

South Asian (SAS) AF: 0.00 AC: 0 AN: 83048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099068

Other (OTH) AF: 0.0000169 AC: 1 AN: 59338

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152302 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74476

African (AFR) AF: 0.0000481 AC: 2 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000680 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000421 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.12
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.43	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.71	N
PhyloP100		0.72
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.49	N
REVEL	Benign	0.026
Sift	Benign	0.080	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.16
MVP		0.44
MPC		0.89
ClinPred		0.089	T
GERP RS		2.5
PromoterAI		-0.0036	Neutral
Varity_R		0.035
gMVP		0.34
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: rs200764199; hg19: chr1-71513214; COSMIC: COSV100138591; COSMIC: COSV100138591;