rs522962

Variant names:

• chr20-49526825-T-C
• rs522962
• NM_000961.4:c.674-2586A>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.674-2586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 152,086 control chromosomes in the GnomAD database, including 29,954 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 0.61 (29954 hom., cov: 32)
• Consequence: PTGIS NM_000961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGIS	NM_000961.4	MANE Select	c.674-2586A>G		intron	N/A	NP_000952.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGIS	ENST00000244043.5	TSL:1 MANE Select	c.674-2586A>G		intron	N/A	ENSP00000244043.3
	PTGIS	ENST00000478971.1	TSL:1	n.495-2586A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.605 AC: 92010 AN: 151968 Hom.: 29898 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.606 AC: 92129 AN: 152086 Hom.: 29954 Cov.: 32 AF XY: 0.601 AC XY: 44679 AN XY: 74312

African (AFR) AF: 0.851 AC: 35327 AN: 41528

American (AMR) AF: 0.500 AC: 7632 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2331 AN: 3470

East Asian (EAS) AF: 0.302 AC: 1561 AN: 5172

South Asian (SAS) AF: 0.585 AC: 2815 AN: 4814

European-Finnish (FIN) AF: 0.485 AC: 5122 AN: 10562

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35384 AN: 67948

Other (OTH) AF: 0.624 AC: 1318 AN: 2112

Alfa AF: 0.548 Hom.: 45184

Bravo AF: 0.613

Asia WGS AF: 0.452 AC: 1576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.47
DANN	Benign	0.37
PhyloP100		-2.0
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: rs522962; hg19: chr20-48143362;