chr1-186677191-A-C

Variant names:

• chr1-186677191-A-C
• rs20432
• NM_000963.4:c.640-275T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000963.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	NM_000963.4	MANE Select	c.640-275T>G		intron	N/A	NP_000954.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	ENST00000367468.10	TSL:1 MANE Select	c.640-275T>G		intron	N/A	ENSP00000356438.5
	PTGS2	ENST00000490885.6	TSL:1	n.773-275T>G		intron	N/A
	PTGS2	ENST00000559627.1	TSL:1	n.*38-275T>G		intron	N/A	ENSP00000454130.1

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

African (AFR) AF: 0.552 AC: 22837 AN: 41402

American (AMR) AF: 0.199 AC: 3033 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 807 AN: 3470

East Asian (EAS) AF: 0.0486 AC: 252 AN: 5190

South Asian (SAS) AF: 0.195 AC: 940 AN: 4822

European-Finnish (FIN) AF: 0.0828 AC: 873 AN: 10544

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10438 AN: 67980

Other (OTH) AF: 0.259 AC: 548 AN: 2116

Alfa AF: 0.180 Hom.: 903

Bravo AF: 0.283

Asia WGS AF: 0.185 AC: 637 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.96
DANN	Benign	0.62
PhyloP100		-0.98
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: rs20432; hg19: chr1-186646323;