20-49566593-T-C

Variant names:

• chr20-49566593-T-C
• rs493694
• NM_000961.4:c.74+1450A>G

Variant summary

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

The NM_000961.4(PTGIS):​c.74+1450A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,076 control chromosomes in the GnomAD database, including 16,220 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 0.45 (16220 hom., cov: 33)
• Consequence: PTGIS NM_000961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 11 publications found

Genes affected

PTGIS (HGNC:9603): (prostaglandin I2 synthase) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostglandin H2 to prostacyclin (prostaglandin I2), a potent vasodilator and inhibitor of platelet aggregation. An imbalance of prostacyclin and its physiological antagonist thromboxane A2 contribute to the development of myocardial infarction, stroke, and atherosclerosis. [provided by RefSeq, Jul 2008]

PTGIS Gene-Disease associations (from GenCC):

• essential hypertension, genetic

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000961.4. 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
	PTGIS	NM_000961.4	MANE Select	c.74+1450A>G		intron	N/A	NP_000952.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGIS	ENST00000244043.5	TSL:1 MANE Select	c.74+1450A>G		intron	N/A	ENSP00000244043.3
	PTGIS	ENST00000478971.1	TSL:1	n.74+1450A>G		intron	N/A
	PTGIS	ENST00000918261.1		c.74+1450A>G		intron	N/A	ENSP00000588320.1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69093 AN: 151958 Hom.: 16220 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.454 AC: 69104 AN: 152076 Hom.: 16220 Cov.: 33 AF XY: 0.456 AC XY: 33909 AN XY: 74334

African (AFR) AF: 0.345 AC: 14294 AN: 41488

American (AMR) AF: 0.462 AC: 7049 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1283 AN: 3472

East Asian (EAS) AF: 0.623 AC: 3223 AN: 5176

South Asian (SAS) AF: 0.495 AC: 2386 AN: 4820

European-Finnish (FIN) AF: 0.500 AC: 5279 AN: 10562

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34172 AN: 67974

Other (OTH) AF: 0.448 AC: 948 AN: 2114

Alfa AF: 0.488 Hom.: 31008

Bravo AF: 0.448

Asia WGS AF: 0.540 AC: 1881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.52
PhyloP100		0.016
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: rs493694; hg19: chr20-48183130; COSMIC: COSV107296526;