rs5275

chr1-186673926-A-Gchr1-186673926-A-T

Variant summary

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

The NM_000963.4(PTGS2):c.*427T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,406 control chromosomes in the GnomAD database, including 13,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency:
  • Genomes: 𝑓 0.40 (13771 hom., cov: 33)
  • Exomes 𝑓: 0.35 (18 hom.)
• Consequence: PTGS2 NM_000963.4 3_prime_UTR
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: -1.15

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS2	NM_000963.4	c.*427T>C		3_prime_UTR_variant	10/10	ENST00000367468.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS2	ENST00000367468.10	c.*427T>C		3_prime_UTR_variant	10/10	1	NM_000963.4	P1
PTGS2	ENST00000490885.6	n.2657T>C		non_coding_transcript_exon_variant	9/9	1
PTGS2	ENST00000680451.1	c.*427T>C		3_prime_UTR_variant	11/11			P1
PTGS2	ENST00000681605.1	c.*1914T>C		3_prime_UTR_variant, NMD_transcript_variant	10/10

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61413 AN: 151922 Hom.: 13726 Cov.: 33

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.365

GnomAD4 exome AF: 0.347 AC: 127 AN: 366 Hom.: 18 Cov.: 0 AF XY: 0.357 AC XY: 80 AN XY: 224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.405 AC: 61514 AN: 152040 Hom.: 13771 Cov.: 33 AF XY: 0.398 AC XY: 29605 AN XY: 74330

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.366

Alfa AF: 0.350 Hom.: 13597

Bravo AF: 0.412

Asia WGS AF: 0.336 AC: 1165 AN: 3468

ClinVar

Significance: other

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Cholangiocarcinoma Other:1

other, no assertion criteria provided

research

Department of Surgery, Campus Charité Mitte Campus Virchow-klinikum, Charite-Universitaetsmedizin Berlin

Dec 10, 2022

No association with disease-free or overall survival after resection of intrahepatic Cholangiocarcinoma No association with disease-free or overall survival

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.96
Dann	Benign	0.38

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: rs5275; hg19: chr1-186643058;