NM_000956.4:c.844-1439A>G

Variant names:

• chr14-52325782-A-G
• rs708498
• NM_000956.4:c.844-1439A>G

Variant summary

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

The NM_000956.4(PTGER2):​c.844-1439A>G variant causes a intron change. The variant allele was found at a frequency of 0.7 in 152,118 control chromosomes in the GnomAD database, including 39,170 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 0.70 (39170 hom., cov: 32)
• Consequence: PTGER2 NM_000956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91
• Publications: 11 publications found

Genes affected

PTGER2 (HGNC:9594): (prostaglandin E receptor 2) This gene encodes a receptor for prostaglandin E2, a metabolite of arachidonic acid which has different biologic activities in a wide range of tissues. Mutations in this gene are associated with aspirin-induced susceptibility to asthma. [provided by RefSeq, Oct 2009]

PTGER2 Gene-Disease associations (from GenCC):

• asthma, nasal polyps, and aspirin intolerance

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGER2	NM_000956.4	c.844-1439A>G		intron_variant	Intron 1 of 1	ENST00000245457.6	NP_000947.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGER2	ENST00000245457.6	c.844-1439A>G		intron_variant	Intron 1 of 1	1	NM_000956.4	ENSP00000245457.5
PTGER2	ENST00000557436.2	c.79-1439A>G		intron_variant	Intron 2 of 2	3		ENSP00000450933.1

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106415 AN: 152000 Hom.: 39172 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.700 AC: 106453 AN: 152118 Hom.: 39170 Cov.: 32 AF XY: 0.689 AC XY: 51232 AN XY: 74362

African (AFR) AF: 0.504 AC: 20878 AN: 41432

American (AMR) AF: 0.692 AC: 10579 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2809 AN: 3470

East Asian (EAS) AF: 0.428 AC: 2217 AN: 5180

South Asian (SAS) AF: 0.440 AC: 2124 AN: 4822

European-Finnish (FIN) AF: 0.774 AC: 8192 AN: 10588

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57179 AN: 68012

Other (OTH) AF: 0.724 AC: 1533 AN: 2116

Alfa AF: 0.796 Hom.: 80585

Bravo AF: 0.689

Asia WGS AF: 0.478 AC: 1660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Benign	0.71
PhyloP100		3.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs708498; hg19: chr14-52792500;