1-186677348-T-G

Variant names:

• chr1-186677348-T-G
• rs4648274
• NM_000963.4:c.639+301A>C

Variant summary

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

The NM_000963.4(PTGS2):​c.639+301A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 152,218 control chromosomes in the GnomAD database, including 393 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 0.040 (393 hom., cov: 33)
• Consequence: PTGS2 NM_000963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS2	NM_000963.4	c.639+301A>C		intron_variant	Intron 5 of 9	ENST00000367468.10	NP_000954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000367468.10	c.639+301A>C		intron_variant	Intron 5 of 9	1	NM_000963.4	ENSP00000356438.5

Frequencies

GnomAD3 genomes AF: 0.0401 AC: 6102 AN: 152100 Hom.: 390 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.0277

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

GnomAD4 genome AF: 0.0401 AC: 6111 AN: 152218 Hom.: 393 Cov.: 33 AF XY: 0.0386 AC XY: 2875 AN XY: 74428

African (AFR) AF: 0.138 AC: 5732 AN: 41522

American (AMR) AF: 0.0166 AC: 254 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10600

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68004

Other (OTH) AF: 0.0274 AC: 58 AN: 2114

Alfa AF: 0.0163 Hom.: 19

Bravo AF: 0.0462

Asia WGS AF: 0.00636 AC: 22 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.51
PhyloP100		1.6
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: rs4648274; hg19: chr1-186646480;