rs5270

Positions:

• chr1-186680587-G-C

Variant summary

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

The ENST00000680451.1(PTGS2):​c.-114+117C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 406,366 control chromosomes in the GnomAD database, including 47 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 0.012 (36 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (11 hom.)
• Consequence: PTGS2 ENST00000680451.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1838/152250) while in subpopulation AFR AF= 0.0416 (1727/41548). AF 95% confidence interval is 0.0399. There are 36 homozygotes in gnomad4. There are 874 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1838 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.186680587G>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000680451.1	c.-114+117C>G		intron_variant				ENSP00000506242.1
PACERR	ENST00000608917.3	n.-14G>C		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1831 AN: 152132 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00670

GnomAD4 exome AF: 0.00262 AC: 667 AN: 254116 Hom.: 11 Cov.: 0 AF XY: 0.00240 AC XY: 316 AN XY: 131674

Gnomad4 AFR exome AF: 0.0451

Gnomad4 AMR exome AF: 0.00238

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0133

Gnomad4 SAS exome AF: 0.000265

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000504

Gnomad4 OTH exome AF: 0.00466

GnomAD4 genome AF: 0.0121 AC: 1838 AN: 152250 Hom.: 36 Cov.: 32 AF XY: 0.0117 AC XY: 874 AN XY: 74430

Gnomad4 AFR AF: 0.0416

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.00895 Hom.: 1

Bravo AF: 0.0142

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.1
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5270; hg19: chr1-186649719;