rs4898758

Variant names:

• chr14-52270050-A-G
• rs4898758
• NM_000953.3:c.846+1390A>G

Variant summary

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

The NM_000953.3(PTGDR):​c.846+1390A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,112 control chromosomes in the GnomAD database, including 2,557 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 0.17 (2557 hom., cov: 32)
• Consequence: PTGDR NM_000953.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGDR	NM_000953.3	c.846+1390A>G		intron_variant	Intron 1 of 1	ENST00000306051.3	NP_000944.1
PTGDR	NM_001281469.2	c.*46+509A>G		intron_variant	Intron 2 of 2		NP_001268398.1
PTGDR	XM_005267891.5	c.846+1390A>G		intron_variant	Intron 1 of 2		XP_005267948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGDR	ENST00000306051.3	c.846+1390A>G		intron_variant	Intron 1 of 1	1	NM_000953.3	ENSP00000303424.2
PTGDR	ENST00000553372.1	c.*46+509A>G		intron_variant	Intron 2 of 2	3		ENSP00000452408.1
ENSG00000289424	ENST00000726797.1	n.300-505T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26562 AN: 151994 Hom.: 2549 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0468

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.175 AC: 26592 AN: 152112 Hom.: 2557 Cov.: 32 AF XY: 0.175 AC XY: 12987 AN XY: 74384

African (AFR) AF: 0.249 AC: 10343 AN: 41462

American (AMR) AF: 0.134 AC: 2052 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 653 AN: 3468

East Asian (EAS) AF: 0.0469 AC: 243 AN: 5176

South Asian (SAS) AF: 0.202 AC: 973 AN: 4814

European-Finnish (FIN) AF: 0.145 AC: 1535 AN: 10596

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10155 AN: 67994

Other (OTH) AF: 0.186 AC: 393 AN: 2108

Alfa AF: 0.160 Hom.: 3538

Bravo AF: 0.175

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.1
DANN	Benign	0.83
PhyloP100		0.13
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: rs4898758; hg19: chr14-52736768;