rs16870224

Positions:

• chr5-40692838-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGER4	NM_000958.3	c.*460G>A		3_prime_UTR_variant	3/3	ENST00000302472.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGER4	ENST00000302472.4	c.*460G>A		3_prime_UTR_variant	3/3	1	NM_000958.3	P1
TTC33	ENST00000636106.1	c.221+53960C>T		intron_variant		5
TTC33	ENST00000636863.1	c.221+53960C>T		intron_variant		5
TTC33	ENST00000637375.1	c.221+53960C>T		intron_variant		5

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

Gnomad4 AFR exome AF: 0.0193

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.0931

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.124

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

Gnomad4 AFR AF: 0.0269

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0852

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.127

Alfa AF: 0.120 Hom.: 1128

Bravo AF: 0.100

Asia WGS AF: 0.175 AC: 607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	4.8
DANN	Benign	0.81

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: rs16870224; hg19: chr5-40692940; COSMIC: COSV56722884; COSMIC: COSV56722884;