rs4648298

chr1-186672550-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000963.4(PTGS2):c.*1803A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 152,640 control chromosomes in the GnomAD database, including 40 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 0.017 (40 hom., cov: 32)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: PTGS2 NM_000963.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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=-0.74).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0172 (2614/152208) while in subpopulation SAS AF= 0.0247 (119/4826). AF 95% confidence interval is 0.023. There are 40 homozygotes in gnomad4. There are 1280 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 2612 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS2	NM_000963.4	c.*1803A>G		3_prime_UTR_variant	10/10	ENST00000367468.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS2	ENST00000367468.10	c.*1803A>G		3_prime_UTR_variant	10/10	1	NM_000963.4	P1
PTGS2	ENST00000680451.1	c.*1803A>G		3_prime_UTR_variant	11/11			P1
PTGS2	ENST00000681605.1	c.*3290A>G		3_prime_UTR_variant, NMD_transcript_variant	10/10

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2612 AN: 152090 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.00625

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.0259

GnomAD4 exome AF: 0.0139 AC: 6 AN: 432 Hom.: 0 Cov.: 0 AF XY: 0.0154 AC XY: 4 AN XY: 260

Gnomad4 FIN exome AF: 0.0141

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0172 AC: 2614 AN: 152208 Hom.: 40 Cov.: 32 AF XY: 0.0172 AC XY: 1280 AN XY: 74416

Gnomad4 AFR AF: 0.00633

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0247

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.0240

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0197 Hom.: 9

Bravo AF: 0.0163

Asia WGS AF: 0.0130 AC: 44 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	12
Dann	Benign	0.87

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: rs4648298; hg19: chr1-186641682;