1-186680486-G-C

Variant names:

• chr1-186680486-G-C
• rs20424
• ENST00000680451.1:c.-113-83C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000680451.1(PTGS2):​c.-113-83C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 473,838 control chromosomes in the GnomAD database, including 55 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 0.0099 (18 hom., cov: 32)
  • Exomes 𝑓: 0.012 (37 hom.)
• Consequence: PTGS2 ENST00000680451.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 7 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]

PACERR (HGNC:50552): (PTGS2 antisense NFKB1 complex-mediated expression regulator RNA) This gene represents transcription of a long non-coding RNA produced in antisense to the prostaglandin-endoperoxide synthase 2 (PTGS2) gene. This transcript interacts with NF-kB transcriptional regulators to promote expression of PTGS2. [provided by RefSeq, Feb 2015]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BS2: High AC in GnomAd4 at 1512 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000680451.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	NM_000963.4	MANE Select	c.-196C>G		upstream_gene	N/A	NP_000954.1
	PACERR	NR_125801.1		n.-168G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	ENST00000680451.1		c.-113-83C>G		intron	N/A	ENSP00000506242.1
	PACERR	ENST00000608917.4	TSL:6	n.379G>C		non_coding_transcript_exon	Exon 1 of 1
	PTGS2	ENST00000367468.10	TSL:1 MANE Select	c.-196C>G		upstream_gene	N/A	ENSP00000356438.5

Frequencies

GnomAD3 genomes AF: 0.00993 AC: 1511 AN: 152128 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.00773

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.00960

GnomAD4 exome AF: 0.0116 AC: 3721 AN: 321592 Hom.: 37 Cov.: 4 AF XY: 0.0114 AC XY: 1933 AN XY: 169102

African (AFR) AF: 0.00197 AC: 15 AN: 7626

American (AMR) AF: 0.00685 AC: 70 AN: 10212

Ashkenazi Jewish (ASJ) AF: 0.0393 AC: 414 AN: 10532

East Asian (EAS) AF: 0.00 AC: 0 AN: 23360

South Asian (SAS) AF: 0.00547 AC: 138 AN: 25214

European-Finnish (FIN) AF: 0.00995 AC: 252 AN: 25320

Middle Eastern (MID) AF: 0.00539 AC: 8 AN: 1484

European-Non Finnish (NFE) AF: 0.0131 AC: 2597 AN: 198376

Other (OTH) AF: 0.0117 AC: 227 AN: 19468

GnomAD4 genome AF: 0.00993 AC: 1512 AN: 152246 Hom.: 18 Cov.: 32 AF XY: 0.00985 AC XY: 733 AN XY: 74438

African (AFR) AF: 0.00253 AC: 105 AN: 41550

American (AMR) AF: 0.0142 AC: 218 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00458 AC: 22 AN: 4808

European-Finnish (FIN) AF: 0.00773 AC: 82 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 944 AN: 68022

Other (OTH) AF: 0.00950 AC: 20 AN: 2106

Alfa AF: 0.00243 Hom.: 0

Bravo AF: 0.00945

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.76
PhyloP100		1.9
PromoterAI		0.027	Neutral

Splicing

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

Other links and lift over

dbSNP: rs20424; hg19: chr1-186649618;