NM_000963.4:c.*2427C>T

Variant names:

• chr1-186671926-G-A
• rs689470
• NM_000963.4:c.*2427C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 55 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=-0.69).
• 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 rank	MANE	Protein	UniProt
PTGS2	NM_000963.4	c.*2427C>T		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	ENST00000367468.10	c.*2427C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_000963.4	ENSP00000356438.5
PTGS2	ENST00000681605.1	n.*3914C>T		non_coding_transcript_exon_variant	Exon 10 of 10			ENSP00000504900.1
PTGS2	ENST00000680451.1	c.*2427C>T		3_prime_UTR_variant	Exon 11 of 11			ENSP00000506242.1
PTGS2	ENST00000681605.1	n.*3914C>T		3_prime_UTR_variant	Exon 10 of 10			ENSP00000504900.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.139 AC: 21036 AN: 151598 Hom.: 3794 Cov.: 32 AF XY: 0.135 AC XY: 9987 AN XY: 74052

African (AFR) AF: 0.425 AC: 17561 AN: 41368

American (AMR) AF: 0.0620 AC: 944 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.0266 AC: 92 AN: 3464

East Asian (EAS) AF: 0.00679 AC: 35 AN: 5158

South Asian (SAS) AF: 0.0619 AC: 298 AN: 4814

European-Finnish (FIN) AF: 0.0154 AC: 160 AN: 10406

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0243 AC: 1648 AN: 67858

Other (OTH) AF: 0.113 AC: 239 AN: 2106

Alfa AF: 0.0389 Hom.: 1082

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
PhyloP100		0.80
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: rs689470; hg19: chr1-186641058;