ENST00000490885.6:n.2657T>C

Variant names:

• chr1-186673926-A-G
• rs5275
• ENST00000490885.6:n.2657T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000490885.6(PTGS2):​n.2657T>C variant causes a non coding transcript exon 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 ENST00000490885.6 non_coding_transcript_exon
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: -1.15
• Publications: 331 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000490885.6. 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.*427T>C		3_prime_UTR	Exon 10 of 10	NP_000954.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	ENST00000490885.6	TSL:1	n.2657T>C		non_coding_transcript_exon	Exon 9 of 9
	PTGS2	ENST00000367468.10	TSL:1 MANE Select	c.*427T>C		3_prime_UTR	Exon 10 of 10	ENSP00000356438.5
	PTGS2	ENST00000681605.1		n.*1914T>C		non_coding_transcript_exon	Exon 10 of 10	ENSP00000504900.1

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 2 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.341 AC: 105 AN: 308

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.405 AC: 17 AN: 42

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.608 AC: 25184 AN: 41452

American (AMR) AF: 0.319 AC: 4878 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1163 AN: 3464

East Asian (EAS) AF: 0.192 AC: 993 AN: 5174

South Asian (SAS) AF: 0.392 AC: 1893 AN: 4826

European-Finnish (FIN) AF: 0.296 AC: 3125 AN: 10570

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.341 AC: 23202 AN: 67954

Other (OTH) AF: 0.366 AC: 775 AN: 2116

Alfa AF: 0.366 Hom.: 26219

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

Dec 10, 2022

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

Significance: other

Review Status: no assertion criteria provided

Collection Method: research

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.96
DANN	Benign	0.38
PhyloP100		-1.2
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: rs5275; hg19: chr1-186643058;