1-186676795-C-T

Variant names:

• chr1-186676795-C-T
• rs2066826
• NM_000963.4:c.723+38G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 48 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PTGS2	NM_000963.4	c.723+38G>A		intron_variant	Intron 6 of 9	ENST00000367468.10	NP_000954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000367468.10	c.723+38G>A		intron_variant	Intron 6 of 9	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

GnomAD2 exomes AF: 0.141 AC: 34666 AN: 246182 AF XY: 0.137

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 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

African (AFR) AF: 0.331 AC: 10883 AN: 32922

American (AMR) AF: 0.164 AC: 7184 AN: 43718

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5254 AN: 25808

East Asian (EAS) AF: 0.0310 AC: 1227 AN: 39562

South Asian (SAS) AF: 0.133 AC: 11097 AN: 83694

European-Finnish (FIN) AF: 0.0771 AC: 4105 AN: 53224

Middle Eastern (MID) AF: 0.184 AC: 964 AN: 5240

European-Non Finnish (NFE) AF: 0.128 AC: 141033 AN: 1103952

Other (OTH) AF: 0.147 AC: 8791 AN: 59812

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

African (AFR) AF: 0.327 AC: 13519 AN: 41388

American (AMR) AF: 0.163 AC: 2490 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3470

East Asian (EAS) AF: 0.0429 AC: 222 AN: 5172

South Asian (SAS) AF: 0.134 AC: 645 AN: 4806

European-Finnish (FIN) AF: 0.0676 AC: 714 AN: 10564

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8856 AN: 67940

Other (OTH) AF: 0.188 AC: 396 AN: 2112

Alfa AF: 0.168 Hom.: 1114

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
PhyloP100		-1.9
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: rs2066826; hg19: chr1-186645927;