1-70974534-C-T

Variant names:

• chr1-70974534-C-T
• rs2072947
• NM_198719.2:c.1078-146G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198719.2(PTGER3):​c.1078-146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 562,606 control chromosomes in the GnomAD database, including 84,271 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 0.47 (18823 hom., cov: 32)
  • Exomes 𝑓: 0.56 (65448 hom.)
• Consequence: PTGER3 NM_198719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGER3	NM_198719.2	c.1078-146G>A		intron_variant	Intron 2 of 3	ENST00000306666.10	NP_942012.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGER3	ENST00000306666.10	c.1078-146G>A		intron_variant	Intron 2 of 3	1	NM_198719.2	ENSP00000302313.5

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71211 AN: 151918 Hom.: 18812 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.508

GnomAD4 exome AF: 0.557 AC: 228483 AN: 410570 Hom.: 65448 AF XY: 0.562 AC XY: 121928 AN XY: 216964

African (AFR) AF: 0.213 AC: 2348 AN: 11004

American (AMR) AF: 0.659 AC: 10627 AN: 16118

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 6352 AN: 12392

East Asian (EAS) AF: 0.683 AC: 18674 AN: 27326

South Asian (SAS) AF: 0.651 AC: 26693 AN: 41024

European-Finnish (FIN) AF: 0.557 AC: 20394 AN: 36646

Middle Eastern (MID) AF: 0.494 AC: 951 AN: 1926

European-Non Finnish (NFE) AF: 0.539 AC: 129796 AN: 240924

Other (OTH) AF: 0.545 AC: 12648 AN: 23210

GnomAD4 genome AF: 0.469 AC: 71235 AN: 152036 Hom.: 18823 Cov.: 32 AF XY: 0.478 AC XY: 35509 AN XY: 74288

African (AFR) AF: 0.218 AC: 9035 AN: 41468

American (AMR) AF: 0.627 AC: 9574 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1826 AN: 3472

East Asian (EAS) AF: 0.726 AC: 3745 AN: 5158

South Asian (SAS) AF: 0.655 AC: 3151 AN: 4812

European-Finnish (FIN) AF: 0.556 AC: 5868 AN: 10556

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36419 AN: 67982

Other (OTH) AF: 0.509 AC: 1072 AN: 2108

Alfa AF: 0.517 Hom.: 65661

Bravo AF: 0.465

Asia WGS AF: 0.673 AC: 2341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.70
PhyloP100		-0.15
Mutation Taster		=99/1	polymorphism (auto)

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: rs2072947; hg19: chr1-71440217; COSMIC: COSV60689328;