rs689470

chr1-186671926-G-Achr1-186671926-G-Cchr1-186671926-G-T

Variant summary

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

The NM_000963.4(PTGS2):c.*2427C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 151,598 control chromosomes in the GnomAD database, including 3,794 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 0.14 (3794 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PTGS2 NM_000963.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795

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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS2	NM_000963.4	c.*2427C>T		3_prime_UTR_variant	10/10	ENST00000367468.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS2	ENST00000367468.10	c.*2427C>T		3_prime_UTR_variant	10/10	1	NM_000963.4	P1
PTGS2	ENST00000680451.1	c.*2427C>T		3_prime_UTR_variant	11/11			P1
PTGS2	ENST00000681605.1	c.*3914C>T		3_prime_UTR_variant, NMD_transcript_variant	10/10

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20965 AN: 151488 Hom.: 3767 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.0266

Gnomad EAS AF: 0.00677

Gnomad SAS AF: 0.0624

Gnomad FIN AF: 0.0154

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.114

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: 0.139 AC: 21036 AN: 151598 Hom.: 3794 Cov.: 32 AF XY: 0.135 AC XY: 9987 AN XY: 74052

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.0620

Gnomad4 ASJ AF: 0.0266

Gnomad4 EAS AF: 0.00679

Gnomad4 SAS AF: 0.0619

Gnomad4 FIN AF: 0.0154

Gnomad4 NFE AF: 0.0243

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0323 Hom.: 498

Bravo AF: 0.153

Asia WGS AF: 0.0600 AC: 209 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	7.9
Dann	Benign	0.75

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: rs689470; hg19: chr1-186641058;