chr1-186676356-A-G

Position:

• chr1-186676356-A-G

Variant summary

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

The NM_000963.4(PTGS2):​c.970+111T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,437,498 control chromosomes in the GnomAD database, including 11,827 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 0.12 (1253 hom., cov: 33)
  • Exomes 𝑓: 0.12 (10574 hom.)
• Consequence: PTGS2 NM_000963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS2	NM_000963.4	c.970+111T>C		intron_variant		ENST00000367468.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS2	ENST00000367468.10	c.970+111T>C		intron_variant		1	NM_000963.4	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18889 AN: 152158 Hom.: 1244 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0419

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.125 AC: 160052 AN: 1285224 Hom.: 10574 Cov.: 20 AF XY: 0.125 AC XY: 79841 AN XY: 637686

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.0306

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0776

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.124 AC: 18918 AN: 152274 Hom.: 1253 Cov.: 33 AF XY: 0.121 AC XY: 9000 AN XY: 74458

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.0416

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0678

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.145

Alfa AF: 0.0633 Hom.: 81

Bravo AF: 0.130

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.97
DANN	Benign	0.51

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: rs4648276; hg19: chr1-186645488;