rs17125273

Variant names:

• chr14-52274928-G-A
• rs17125273
• NM_000953.3:c.1044G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000953.3(PTGDR):​c.1044G>A​(p.Arg348Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,595,796 control chromosomes in the GnomAD database, including 11,751 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 0.099 (889 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10862 hom.)
• Consequence: PTGDR NM_000953.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 21 publications found

Genes affected

PTGDR (HGNC:9591): (prostaglandin D2 receptor) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) superfamily. The receptors are seven-pass transmembrane proteins that respond to extracellular cues and activate intracellular signal transduction pathways. This protein is reported to be a receptor for prostaglandin D2, which is a mediator of allergic inflammation and allergic airway inflammation in asthma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ENSG00000289424 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=1.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGDR	NM_000953.3	c.1044G>A	p.Arg348Arg	synonymous_variant	Exon 2 of 2	ENST00000306051.3	NP_000944.1
PTGDR	XM_005267891.5	c.1044G>A	p.Arg348Arg	synonymous_variant	Exon 2 of 3		XP_005267948.1
PTGDR	NM_001281469.2	c.*244G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001268398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGDR	ENST00000306051.3	c.1044G>A	p.Arg348Arg	synonymous_variant	Exon 2 of 2	1	NM_000953.3	ENSP00000303424.2
PTGDR	ENST00000553372.1	c.*244G>A		3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000452408.1
ENSG00000289424	ENST00000726797.1	n.300-5383C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0994 AC: 15077 AN: 151738 Hom.: 886 Cov.: 32

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.0909

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.00889

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0958

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.124

GnomAD2 exomes AF: 0.111 AC: 27457 AN: 248436 AF XY: 0.120

Gnomad AFR exome AF: 0.0500

Gnomad AMR exome AF: 0.0652

Gnomad ASJ exome AF: 0.175

Gnomad EAS exome AF: 0.00822

Gnomad FIN exome AF: 0.0942

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.118 AC: 169788 AN: 1443940 Hom.: 10862 Cov.: 32 AF XY: 0.121 AC XY: 87144 AN XY: 719170

African (AFR) AF: 0.0511 AC: 1691 AN: 33102

American (AMR) AF: 0.0664 AC: 2960 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 4494 AN: 25988

East Asian (EAS) AF: 0.00702 AC: 278 AN: 39618

South Asian (SAS) AF: 0.178 AC: 15271 AN: 85680

European-Finnish (FIN) AF: 0.0937 AC: 4992 AN: 53294

Middle Eastern (MID) AF: 0.235 AC: 1350 AN: 5742

European-Non Finnish (NFE) AF: 0.120 AC: 131737 AN: 1096156

Other (OTH) AF: 0.117 AC: 7015 AN: 59770

GnomAD4 genome AF: 0.0993 AC: 15086 AN: 151856 Hom.: 889 Cov.: 32 AF XY: 0.0999 AC XY: 7409 AN XY: 74186

African (AFR) AF: 0.0511 AC: 2116 AN: 41410

American (AMR) AF: 0.0907 AC: 1385 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3464

East Asian (EAS) AF: 0.00891 AC: 46 AN: 5164

South Asian (SAS) AF: 0.167 AC: 803 AN: 4804

European-Finnish (FIN) AF: 0.0958 AC: 1003 AN: 10470

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.127 AC: 8654 AN: 67964

Other (OTH) AF: 0.124 AC: 263 AN: 2114

Alfa AF: 0.122 Hom.: 2754

Bravo AF: 0.0935

Asia WGS AF: 0.0750 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.34
PhyloP100		1.1
Mutation Taster		=100/0	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: rs17125273; hg19: chr14-52741646; COSMIC: COSV60093901;