rs4648291

Positions:

• chr1-186674071-TTATAA-T
• chr1-186674071-TTATAA-TTATAATATAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000963.4(PTGS2):​c.*277_*281del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 171,644 control chromosomes in the GnomAD database, including 3,165 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (3109 hom., cov: 31)
  • Exomes 𝑓: 0.019 (56 hom.)
• Consequence: PTGS2 NM_000963.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGS2	NM_000963.4	c.*277_*281del		3_prime_UTR_variant	10/10	ENST00000367468.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGS2	ENST00000367468.10	c.*277_*281del		3_prime_UTR_variant	10/10	1	NM_000963.4	P1
PTGS2	ENST00000490885.6	n.2507_2511del		non_coding_transcript_exon_variant	9/9	1
PTGS2	ENST00000680451.1	c.*277_*281del		3_prime_UTR_variant	11/11			P1
PTGS2	ENST00000681605.1	c.*1764_*1768del		3_prime_UTR_variant, NMD_transcript_variant	10/10

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17211 AN: 151872 Hom.: 3088 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0430

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.0843

GnomAD4 exome AF: 0.0187 AC: 368 AN: 19654 Hom.: 56 AF XY: 0.0158 AC XY: 170 AN XY: 10738

Gnomad4 AFR exome AF: 0.402

Gnomad4 AMR exome AF: 0.0297

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000650

Gnomad4 SAS exome AF: 0.0490

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00157

Gnomad4 OTH exome AF: 0.0439

GnomAD4 genome AF: 0.114 AC: 17271 AN: 151990 Hom.: 3109 Cov.: 31 AF XY: 0.110 AC XY: 8151 AN XY: 74360

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.0430

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.0369

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00185

Gnomad4 OTH AF: 0.0834

Alfa AF: 0.0938 Hom.: 256

Bravo AF: 0.130

Asia WGS AF: 0.0430 AC: 150 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4648291; hg19: chr1-186643203;