1-186672065-C-T

Variant names:

• chr1-186672065-C-T
• rs689469
• NM_000963.4:c.*2288G>A

Variant summary

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

The NM_000963.4(PTGS2):​c.*2288G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 151,718 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 0.016 (40 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PTGS2 NM_000963.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478

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=-0.83).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0165 (2500/151718) while in subpopulation SAS AF= 0.0249 (120/4816). AF 95% confidence interval is 0.0217. There are 40 homozygotes in gnomad4. There are 1237 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2500 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS2	NM_000963.4	c.*2288G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000367468.10	NP_000954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000367468	c.*2288G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_000963.4	ENSP00000356438.5
PTGS2	ENST00000680451	c.*2288G>A		3_prime_UTR_variant	Exon 11 of 11			ENSP00000506242.1
PTGS2	ENST00000681605.1	n.*3775G>A		non_coding_transcript_exon_variant	Exon 10 of 10			ENSP00000504900.1
PTGS2	ENST00000681605.1	n.*3775G>A		3_prime_UTR_variant	Exon 10 of 10			ENSP00000504900.1

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2498 AN: 151602 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.00588

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.0243

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.0249

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0227

Gnomad OTH AF: 0.0250

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0165 AC: 2500 AN: 151718 Hom.: 40 Cov.: 32 AF XY: 0.0167 AC XY: 1237 AN XY: 74112

Gnomad4 AFR AF: 0.00596

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.0243

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0249

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.0226

Gnomad4 OTH AF: 0.0247

Alfa AF: 0.00944 Hom.: 6

Bravo AF: 0.0155

Asia WGS AF: 0.0130 AC: 46 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.79
DANN	Benign	0.57

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: rs689469; hg19: chr1-186641197;