chr1-186672550-T-C

Variant names:

• chr1-186672550-T-C
• rs4648298
• NM_000963.4:c.*1803A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000963.4(PTGS2):​c.*1803A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 152,640 control chromosomes in the GnomAD database, including 40 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 0.017 (40 hom., cov: 32)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: PTGS2 NM_000963.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 26 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=-0.74).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0172 (2614/152208) while in subpopulation SAS AF = 0.0247 (119/4826). AF 95% confidence interval is 0.023. There are 40 homozygotes in GnomAd4. There are 1280 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2614 AD gene.

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.*1803A>G		3_prime_UTR	Exon 10 of 10	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.*1803A>G		3_prime_UTR	Exon 10 of 10	ENSP00000356438.5	P35354
	PTGS2	ENST00000680451.1		c.*1803A>G		3_prime_UTR	Exon 11 of 11	ENSP00000506242.1	P35354
	PTGS2	ENST00000681605.1		n.*3290A>G		non_coding_transcript_exon	Exon 10 of 10	ENSP00000504900.1	A0A7P0T828

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2612 AN: 152090 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.00625

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.0259

GnomAD4 exome AF: 0.0139 AC: 6 AN: 432 Hom.: 0 Cov.: 0 AF XY: 0.0154 AC XY: 4 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0141 AC: 6 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0172 AC: 2614 AN: 152208 Hom.: 40 Cov.: 32 AF XY: 0.0172 AC XY: 1280 AN XY: 74416

African (AFR) AF: 0.00633 AC: 263 AN: 41558

American (AMR) AF: 0.0157 AC: 240 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 84 AN: 3466

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5190

South Asian (SAS) AF: 0.0247 AC: 119 AN: 4826

European-Finnish (FIN) AF: 0.0153 AC: 162 AN: 10608

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0240 AC: 1629 AN: 67954

Other (OTH) AF: 0.0256 AC: 54 AN: 2110

Alfa AF: 0.0201 Hom.: 16

Bravo AF: 0.0163

Asia WGS AF: 0.0130 AC: 44 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

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: rs4648298; hg19: chr1-186641682;