14-52274253-A-G

Position:

• chr14-52274253-A-G

Variant summary

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

The NM_000953.3(PTGDR):​c.847-478A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,072 control chromosomes in the GnomAD database, including 10,070 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 0.35 (10070 hom., cov: 32)
• Consequence: PTGDR NM_000953.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGDR	NM_000953.3	c.847-478A>G		intron_variant		ENST00000306051.3	NP_000944.1
PTGDR	NM_001281469.2	c.*47-478A>G		intron_variant			NP_001268398.1
PTGDR	XM_005267891.5	c.847-478A>G		intron_variant			XP_005267948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGDR	ENST00000306051.3	c.847-478A>G		intron_variant		1	NM_000953.3	ENSP00000303424	P1
PTGDR	ENST00000553372.1	c.*47-478A>G		intron_variant		3		ENSP00000452408

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53688 AN: 151954 Hom.: 10067 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.353 AC: 53717 AN: 152072 Hom.: 10070 Cov.: 32 AF XY: 0.350 AC XY: 26025 AN XY: 74334

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.397

Alfa AF: 0.418 Hom.: 12996

Bravo AF: 0.341

Asia WGS AF: 0.265 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.1
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs708486; hg19: chr14-52740971; COSMIC: COSV60095226;