1-186677191-A-C

Position:

• chr1-186677191-A-C

Variant summary

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

The NM_000963.4(PTGS2):​c.640-275T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,990 control chromosomes in the GnomAD database, including 7,797 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 0.26 (7797 hom., cov: 33)
• Consequence: PTGS2 NM_000963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.980

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS2	NM_000963.4	c.640-275T>G		intron_variant		ENST00000367468.10	NP_000954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000367468.10	c.640-275T>G		intron_variant		1	NM_000963.4	ENSP00000356438	P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39767 AN: 151872 Hom.: 7754 Cov.: 33

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0488

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0828

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.262 AC: 39869 AN: 151990 Hom.: 7797 Cov.: 33 AF XY: 0.255 AC XY: 18939 AN XY: 74328

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.0486

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.0828

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.259

Alfa AF: 0.210 Hom.: 707

Bravo AF: 0.283

Asia WGS AF: 0.185 AC: 637 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.96
DANN	Benign	0.62

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: rs20432; hg19: chr1-186646323;