14-52274253-A-T

Variant names:

• chr14-52274253-A-T
• rs708486
• NM_000953.3:c.847-478A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000953.3(PTGDR):​c.847-478A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: PTGDR NM_000953.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGDR	NM_000953.3	c.847-478A>T		intron_variant	Intron 1 of 1	ENST00000306051.3	NP_000944.1
PTGDR	NM_001281469.2	c.*47-478A>T		intron_variant	Intron 2 of 2		NP_001268398.1
PTGDR	XM_005267891.5	c.847-478A>T		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.847-478A>T		intron_variant	Intron 1 of 1	1	NM_000953.3	ENSP00000303424.2
PTGDR	ENST00000553372.1	c.*47-478A>T		intron_variant	Intron 2 of 2	3		ENSP00000452408.1
ENSG00000289424	ENST00000726797.1	n.300-4708T>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 15703

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.7
DANN	Benign	0.45
PhyloP100		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs708486; hg19: chr14-52740971;