1-186671571-G-T

Variant names:

• chr1-186671571-G-T
• rs4648307
• NM_000963.4:c.*2782C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000963.4(PTGS2):​c.*2782C>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 151,852 control chromosomes in the GnomAD database, including 1,243 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 0.12 (1243 hom., cov: 32)
• Consequence: PTGS2 NM_000963.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 9 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000963.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	NM_000963.4	MANE Select	c.*2782C>A		downstream_gene	N/A	NP_000954.1	P35354

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	ENST00000367468.10	TSL:1 MANE Select	c.*2782C>A		downstream_gene	N/A	ENSP00000356438.5	P35354
	PTGS2	ENST00000680451.1		c.*2782C>A		downstream_gene	N/A	ENSP00000506242.1	P35354
	PTGS2	ENST00000681605.1		n.*4269C>A		downstream_gene	N/A	ENSP00000504900.1	A0A7P0T828

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18796 AN: 151734 Hom.: 1234 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0416

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0675

Gnomad MID AF: 0.183

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.142

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.124 AC: 18826 AN: 151852 Hom.: 1243 Cov.: 32 AF XY: 0.121 AC XY: 8968 AN XY: 74224

African (AFR) AF: 0.131 AC: 5441 AN: 41396

American (AMR) AF: 0.135 AC: 2052 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 712 AN: 3464

East Asian (EAS) AF: 0.0413 AC: 214 AN: 5184

South Asian (SAS) AF: 0.132 AC: 634 AN: 4802

European-Finnish (FIN) AF: 0.0675 AC: 712 AN: 10552

Middle Eastern (MID) AF: 0.179 AC: 52 AN: 290

European-Non Finnish (NFE) AF: 0.128 AC: 8674 AN: 67894

Other (OTH) AF: 0.146 AC: 308 AN: 2112

Alfa AF: 0.0844 Hom.: 180

Bravo AF: 0.130

Asia WGS AF: 0.125 AC: 434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.59
PhyloP100		1.7

Splicing

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

Other links and lift over

dbSNP: rs4648307; hg19: chr1-186640703;