14-52273723-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000953.3(PTGDR):c.847-1008C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,182 control chromosomes in the GnomAD database, including 3,563 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 0.19 (3563 hom., cov: 32)
• Consequence: PTGDR NM_000953.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGDR	NM_000953.3	c.847-1008C>G		intron_variant		ENST00000306051.3
PTGDR	NM_001281469.2	c.*47-1008C>G		intron_variant
PTGDR	XM_005267891.5	c.847-1008C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGDR	ENST00000306051.3	c.847-1008C>G		intron_variant		1	NM_000953.3	P1
PTGDR	ENST00000553372.1	c.*47-1008C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29685 AN: 152064 Hom.: 3567 Cov.: 32

Gnomad AFR AF: 0.0669

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.195 AC: 29669 AN: 152182 Hom.: 3563 Cov.: 32 AF XY: 0.192 AC XY: 14311 AN XY: 74394

Gnomad4 AFR AF: 0.0667

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.225

Alfa AF: 0.134 Hom.: 279

Bravo AF: 0.182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.1
Dann	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs10498445; hg19: chr14-52740441;