chr1-70862400-A-G

Variant names:

• chr1-70862400-A-G
• rs5703
• ENST00000370931.7:c.*24-9541T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

ENSG00000235782 (HGNC:40481):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGER3	NM_198714.2	c.*24-9541T>C		intron_variant	Intron 4 of 4		NP_942007.1
PTGER3	NM_198716.2	c.1105-9541T>C		intron_variant	Intron 3 of 3		NP_942009.1
PTGER3	NM_198717.2	c.1078-9541T>C		intron_variant	Intron 2 of 2		NP_942010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGER3	ENST00000370931.7	c.*24-9541T>C		intron_variant	Intron 4 of 4	1		ENSP00000359969.3
PTGER3	ENST00000460330.5	c.1105-9541T>C		intron_variant	Intron 3 of 3	1		ENSP00000418073.1
PTGER3	ENST00000628037.2	c.1078-9541T>C		intron_variant	Intron 2 of 2	1		ENSP00000486617.1

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

GnomAD2 exomes AF: 0.00313 AC: 777 AN: 248474 AF XY: 0.00219

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 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

African (AFR) AF: 0.0465 AC: 1213 AN: 26088

American (AMR) AF: 0.00150 AC: 56 AN: 37266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16852

East Asian (EAS) AF: 0.0000596 AC: 1 AN: 16772

South Asian (SAS) AF: 0.000120 AC: 10 AN: 83004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32402

Middle Eastern (MID) AF: 0.00157 AC: 7 AN: 4464

European-Non Finnish (NFE) AF: 0.0000391 AC: 37 AN: 946774

Other (OTH) AF: 0.00208 AC: 91 AN: 43756

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

African (AFR) AF: 0.0434 AC: 1804 AN: 41532

American (AMR) AF: 0.00431 AC: 66 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68020

Other (OTH) AF: 0.00900 AC: 19 AN: 2112

Alfa AF: 0.00478 Hom.: 19

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
PhyloP100		1.1
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs5703; hg19: chr1-71328083;