rs16870224

Variant names:

• chr5-40692838-G-A
• rs16870224
• NM_000958.3:c.*460G>A

Variant summary

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

The NM_000958.3(PTGER4):​c.*460G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 985,214 control chromosomes in the GnomAD database, including 6,500 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 0.099 (945 hom., cov: 32)
  • Exomes 𝑓: 0.11 (5555 hom.)
• Consequence: PTGER4 NM_000958.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 14 publications found

Genes affected

PTGER4 (HGNC:9596): (prostaglandin E receptor 4) The protein encoded by this gene is a member of the G-protein coupled receptor family. This protein is one of four receptors identified for prostaglandin E2 (PGE2). This receptor can activate T-cell factor signaling. It has been shown to mediate PGE2 induced expression of early growth response 1 (EGR1), regulate the level and stability of cyclooxygenase-2 mRNA, and lead to the phosphorylation of glycogen synthase kinase-3. Knockout studies in mice suggest that this receptor may be involved in the neonatal adaptation of circulatory system, osteoporosis, as well as initiation of skin immune responses. [provided by RefSeq, Jul 2008]

TTC33 (HGNC:29959): (tetratricopeptide repeat domain 33)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000958.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGER4	NM_000958.3	MANE Select	c.*460G>A		3_prime_UTR	Exon 3 of 3	NP_000949.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGER4	ENST00000302472.4	TSL:1 MANE Select	c.*460G>A		3_prime_UTR	Exon 3 of 3	ENSP00000302846.3
	TTC33	ENST00000637375.1	TSL:5	c.221+53960C>T		intron	N/A	ENSP00000490134.1
	TTC33	ENST00000636863.1	TSL:5	c.221+53960C>T		intron	N/A	ENSP00000490389.1

Frequencies

GnomAD3 genomes AF: 0.0991 AC: 15050 AN: 151910 Hom.: 944 Cov.: 32

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0852

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.114 AC: 94982 AN: 833186 Hom.: 5555 Cov.: 28 AF XY: 0.114 AC XY: 43908 AN XY: 384914

African (AFR) AF: 0.0193 AC: 304 AN: 15758

American (AMR) AF: 0.130 AC: 144 AN: 1106

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 911 AN: 5146

East Asian (EAS) AF: 0.244 AC: 920 AN: 3774

South Asian (SAS) AF: 0.109 AC: 1786 AN: 16456

European-Finnish (FIN) AF: 0.0931 AC: 67 AN: 720

Middle Eastern (MID) AF: 0.140 AC: 227 AN: 1616

European-Non Finnish (NFE) AF: 0.115 AC: 87237 AN: 761322

Other (OTH) AF: 0.124 AC: 3386 AN: 27288

GnomAD4 genome AF: 0.0990 AC: 15058 AN: 152028 Hom.: 945 Cov.: 32 AF XY: 0.0986 AC XY: 7328 AN XY: 74304

African (AFR) AF: 0.0269 AC: 1116 AN: 41484

American (AMR) AF: 0.124 AC: 1897 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3470

East Asian (EAS) AF: 0.250 AC: 1292 AN: 5166

South Asian (SAS) AF: 0.132 AC: 634 AN: 4816

European-Finnish (FIN) AF: 0.0852 AC: 899 AN: 10548

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8222 AN: 67954

Other (OTH) AF: 0.127 AC: 269 AN: 2110

Alfa AF: 0.119 Hom.: 1350

Bravo AF: 0.100

Asia WGS AF: 0.175 AC: 607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	4.8
DANN	Benign	0.81
PhyloP100		-0.35
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: rs16870224; hg19: chr5-40692940; COSMIC: COSV56722884; COSMIC: COSV56722884;