rs5703

chr1-70862400-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000370931.7(PTGER3):c.*24-9541T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,359,638 control chromosomes in the GnomAD database, including 74 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 0.012 (45 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (29 hom.)
• Consequence: PTGER3 ENST00000370931.7 intron
• Scores: Splicing: ADA: 0.00001375
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1899/152260) while in subpopulation AFR AF= 0.0434 (1804/41532). AF 95% confidence interval is 0.0418. There are 45 homozygotes in gnomad4. There are 910 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 45 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGER3	NM_198714.2	c.*24-9541T>C		intron_variant
PTGER3	NM_198716.2	c.1105-9541T>C		intron_variant
PTGER3	NM_198717.2	c.1078-9541T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGER3	ENST00000370931.7	c.*24-9541T>C		intron_variant		1		A1
PTGER3	ENST00000460330.5	c.1105-9541T>C		intron_variant		1		A2
PTGER3	ENST00000628037.2	c.1078-9541T>C		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1895 AN: 152142 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.0435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00909

GnomAD3 exomes AF: 0.00313 AC: 777 AN: 248474 Hom.: 17 AF XY: 0.00219 AC XY: 295 AN XY: 134498

Gnomad AFR exome AF: 0.0435

Gnomad AMR exome AF: 0.00151

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000720

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00117 AC: 1415 AN: 1207378 Hom.: 29 Cov.: 27 AF XY: 0.000930 AC XY: 557 AN XY: 598882

Gnomad4 AFR exome AF: 0.0465

Gnomad4 AMR exome AF: 0.00150

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000596

Gnomad4 SAS exome AF: 0.000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000391

Gnomad4 OTH exome AF: 0.00208

GnomAD4 genome AF: 0.0125 AC: 1899 AN: 152260 Hom.: 45 Cov.: 32 AF XY: 0.0122 AC XY: 910 AN XY: 74460

Gnomad4 AFR AF: 0.0434

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00348 Hom.: 11

Bravo AF: 0.0141

Asia WGS AF: 0.00318 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.6
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0020

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5703; hg19: chr1-71328083;