rs4648287

Positions:

• chr1-186674818-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.1406-56T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00825 in 1,510,052 control chromosomes in the GnomAD database, including 893 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 0.043 (464 hom., cov: 33)
  • Exomes 𝑓: 0.0044 (429 hom.)
• Consequence: PTGS2 NM_000963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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 (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS2	NM_000963.4	c.1406-56T>C		intron_variant		ENST00000367468.10	NP_000954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000367468.10	c.1406-56T>C		intron_variant		1	NM_000963.4	ENSP00000356438	P1

Frequencies

GnomAD3 genomes AF: 0.0427 AC: 6497 AN: 152190 Hom.: 454 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.00437 AC: 5929 AN: 1357744 Hom.: 429 AF XY: 0.00388 AC XY: 2596 AN XY: 669502

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.00624

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000518

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000263

Gnomad4 OTH exome AF: 0.00888

GnomAD4 genome AF: 0.0429 AC: 6534 AN: 152308 Hom.: 464 Cov.: 33 AF XY: 0.0409 AC XY: 3045 AN XY: 74482

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0130

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0354 Hom.: 32

Bravo AF: 0.0482

Asia WGS AF: 0.0110 AC: 39 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	0.48
DANN	Benign	0.33

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: rs4648287; hg19: chr1-186643950;