chr1-186676537-A-G

Variant names:

• chr1-186676537-A-G
• rs5278
• NM_000963.4:c.900T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000963.4(PTGS2):​c.900T>C​(p.Asp300Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00348 in 1,614,096 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (80 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (74 hom.)
• Consequence: PTGS2 NM_000963.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0270
• Publications: 11 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 1-186676537-A-G is Benign according to our data. Variant chr1-186676537-A-G is described in ClinVar as Benign. ClinVar VariationId is 780291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.027 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.057 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.900T>C	p.Asp300Asp	synonymous	Exon 7 of 10	NP_000954.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	ENST00000367468.10	TSL:1 MANE Select	c.900T>C	p.Asp300Asp	synonymous	Exon 7 of 10	ENSP00000356438.5
	PTGS2	ENST00000490885.6	TSL:1	n.1033T>C		non_coding_transcript_exon	Exon 7 of 9
	PTGS2	ENST00000559627.1	TSL:1	n.*298T>C		non_coding_transcript_exon	Exon 7 of 10	ENSP00000454130.1

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2627 AN: 152084 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.0591

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00754

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00406

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00483 AC: 1214 AN: 251488 AF XY: 0.00341

Gnomad AFR exome AF: 0.0609

Gnomad AMR exome AF: 0.00306

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00440

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00205 AC: 2994 AN: 1461894 Hom.: 74 Cov.: 32 AF XY: 0.00173 AC XY: 1258 AN XY: 727248

African (AFR) AF: 0.0602 AC: 2017 AN: 33480

American (AMR) AF: 0.00360 AC: 161 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0106 AC: 420 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.0000800 AC: 89 AN: 1112012

Other (OTH) AF: 0.00472 AC: 285 AN: 60396

GnomAD4 genome AF: 0.0173 AC: 2628 AN: 152202 Hom.: 80 Cov.: 32 AF XY: 0.0166 AC XY: 1238 AN XY: 74404

African (AFR) AF: 0.0589 AC: 2447 AN: 41514

American (AMR) AF: 0.00753 AC: 115 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00407 AC: 21 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68018

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.00705 Hom.: 22

Bravo AF: 0.0205

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.3
DANN	Benign	0.62
PhyloP100		-0.027
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: rs5278; hg19: chr1-186645669; COSMIC: COSV66569644; COSMIC: COSV66569644;