rs2066826

Positions:

• chr1-186676795-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000963.4(PTGS2):​c.723+38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,599,858 control chromosomes in the GnomAD database, including 17,101 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 0.18 (3245 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13856 hom.)
• Consequence: PTGS2 NM_000963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

Genes affected

PTGS2 (HGNC:9605): (prostaglandin-endoperoxide synthase 2) Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase, is the key enzyme in prostaglandin biosynthesis, and acts both as a dioxygenase and as a peroxidase. There are two isozymes of PTGS: a constitutive PTGS1 and an inducible PTGS2, which differ in their regulation of expression and tissue distribution. This gene encodes the inducible isozyme. It is regulated by specific stimulatory events, suggesting that it is responsible for the prostanoid biosynthesis involved in inflammation and mitogenesis. [provided by RefSeq, Feb 2009]

PTGS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS2	NM_000963.4	c.723+38G>A		intron_variant		ENST00000367468.10	NP_000954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000367468.10	c.723+38G>A		intron_variant		1	NM_000963.4	ENSP00000356438.5

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27611 AN: 151808 Hom.: 3231 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0432

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0676

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.184

GnomAD3 exomes AF: 0.141 AC: 34666 AN: 246182 Hom.: 2960 AF XY: 0.137 AC XY: 18312 AN XY: 133270

Gnomad AFR exome AF: 0.329

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.0402

Gnomad SAS exome AF: 0.137

Gnomad FIN exome AF: 0.0735

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.132 AC: 190538 AN: 1447932 Hom.: 13856 Cov.: 30 AF XY: 0.131 AC XY: 94666 AN XY: 720336

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.0310

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.0771

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.182 AC: 27652 AN: 151926 Hom.: 3245 Cov.: 32 AF XY: 0.177 AC XY: 13128 AN XY: 74258

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.0429

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0676

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.188

Alfa AF: 0.171 Hom.: 811

Bravo AF: 0.197

Asia WGS AF: 0.134 AC: 465 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.018
DANN	Benign	0.60

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: rs2066826; hg19: chr1-186645927;