rs4648306

Variant names:

• chr1-186671572-C-T
• rs4648306
• NM_000963.4:c.*2781G>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.*2781G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 151,982 control chromosomes in the GnomAD database, including 1,243 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 (1243 hom., cov: 32)
• Consequence: PTGS2 NM_000963.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 3 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS2	NM_000963.4	c.*2781G>A		downstream_gene_variant		ENST00000367468.10	NP_000954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000367468.10	c.*2781G>A		downstream_gene_variant		1	NM_000963.4	ENSP00000356438.5
PTGS2	ENST00000680451.1	c.*2781G>A		downstream_gene_variant				ENSP00000506242.1
PTGS2	ENST00000681605.1	n.*4268G>A		downstream_gene_variant				ENSP00000504900.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18796 AN: 151864 Hom.: 1234 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0416

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0674

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.124 AC: 18826 AN: 151982 Hom.: 1243 Cov.: 32 AF XY: 0.121 AC XY: 8968 AN XY: 74324

African (AFR) AF: 0.131 AC: 5440 AN: 41450

American (AMR) AF: 0.134 AC: 2052 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 712 AN: 3464

East Asian (EAS) AF: 0.0413 AC: 214 AN: 5176

South Asian (SAS) AF: 0.131 AC: 634 AN: 4826

European-Finnish (FIN) AF: 0.0674 AC: 713 AN: 10580

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.128 AC: 8674 AN: 67916

Other (OTH) AF: 0.146 AC: 308 AN: 2108

Alfa AF: 0.117 Hom.: 151

Bravo AF: 0.130

Asia WGS AF: 0.125 AC: 434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.8
DANN	Benign	0.49
PhyloP100		0.0080

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4648306; hg19: chr1-186640704;