14-52275462-T-C

Position:

• chr14-52275462-T-C

Variant summary

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

The NM_000953.3(PTGDR):​c.*498T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 156,316 control chromosomes in the GnomAD database, including 496 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 0.069 (483 hom., cov: 32)
  • Exomes 𝑓: 0.073 (13 hom.)
• Consequence: PTGDR NM_000953.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGDR	NM_000953.3	c.*498T>C		3_prime_UTR_variant	2/2	ENST00000306051.3	NP_000944.1
PTGDR	NM_001281469.2	c.*778T>C		3_prime_UTR_variant	3/3		NP_001268398.1
PTGDR	XM_005267891.5	c.*19+479T>C		intron_variant			XP_005267948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGDR	ENST00000306051.3	c.*498T>C		3_prime_UTR_variant	2/2	1	NM_000953.3	ENSP00000303424.2

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 10487 AN: 152138 Hom.: 481 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.0601

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0864

Gnomad OTH AF: 0.0602

GnomAD4 exome AF: 0.0732 AC: 297 AN: 4060 Hom.: 13 Cov.: 0 AF XY: 0.0747 AC XY: 178 AN XY: 2384

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0523

Gnomad4 ASJ exome AF: 0.0417

Gnomad4 EAS exome AF: 0.0676

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.0714

Gnomad4 NFE exome AF: 0.0718

Gnomad4 OTH exome AF: 0.0714

GnomAD4 genome AF: 0.0689 AC: 10494 AN: 152256 Hom.: 483 Cov.: 32 AF XY: 0.0699 AC XY: 5207 AN XY: 74440

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.0601

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0670

Gnomad4 NFE AF: 0.0864

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0848 Hom.: 678

Bravo AF: 0.0660

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.75

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: rs17831682; hg19: chr14-52742180;