1-186680486-G-C

Position:

• chr1-186680486-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 -8 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000680451.1	c.-113-83C>G		intron_variant				ENSP00000506242	P1

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

Gnomad4 AFR exome AF: 0.00197

Gnomad4 AMR exome AF: 0.00685

Gnomad4 ASJ exome AF: 0.0393

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00547

Gnomad4 FIN exome AF: 0.00995

Gnomad4 NFE exome AF: 0.0131

Gnomad4 OTH exome AF: 0.0117

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

Gnomad4 AFR AF: 0.00253

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00458

Gnomad4 FIN AF: 0.00773

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.00950

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs20424; hg19: chr1-186649618;