rs12587410

Variant names:

• chr14-52323817-C-T
• rs12587410
• NM_000956.4:c.844-3404C>T

Variant summary

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

The NM_000956.4(PTGER2):​c.844-3404C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0735 in 152,214 control chromosomes in the GnomAD database, including 576 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 0.073 (576 hom., cov: 32)
• Consequence: PTGER2 NM_000956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGER2	NM_000956.4	c.844-3404C>T		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.844-3404C>T		intron_variant	Intron 1 of 1	1	NM_000956.4	ENSP00000245457.5
PTGER2	ENST00000557436.2	c.79-3404C>T		intron_variant	Intron 2 of 2	3		ENSP00000450933.1

Frequencies

GnomAD3 genomes AF: 0.0733 AC: 11153 AN: 152096 Hom.: 572 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0799

Gnomad ASJ AF: 0.0475

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.0286

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0331

Gnomad OTH AF: 0.0675

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

GnomAD4 genome AF: 0.0735 AC: 11181 AN: 152214 Hom.: 576 Cov.: 32 AF XY: 0.0750 AC XY: 5581 AN XY: 74430

African (AFR) AF: 0.138 AC: 5714 AN: 41524

American (AMR) AF: 0.0804 AC: 1230 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0475 AC: 165 AN: 3472

East Asian (EAS) AF: 0.162 AC: 837 AN: 5174

South Asian (SAS) AF: 0.0923 AC: 445 AN: 4822

European-Finnish (FIN) AF: 0.0286 AC: 303 AN: 10604

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0331 AC: 2251 AN: 68004

Other (OTH) AF: 0.0672 AC: 142 AN: 2112

Alfa AF: 0.0577 Hom.: 64

Bravo AF: 0.0801

Asia WGS AF: 0.139 AC: 482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.53
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12587410; hg19: chr14-52790535;