20-49559061-C-T

Variant names:

• chr20-49559061-C-T
• rs6125671
• NM_000961.4:c.75-8872G>A

Variant summary

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

The NM_000961.4(PTGIS):​c.75-8872G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,952 control chromosomes in the GnomAD database, including 5,637 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 0.25 (5637 hom., cov: 31)
• Consequence: PTGIS NM_000961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• Publications: 10 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 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.75-8872G>A		intron	N/A	NP_000952.1	Q16647

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGIS	ENST00000244043.5	TSL:1 MANE Select	c.75-8872G>A		intron	N/A	ENSP00000244043.3	Q16647
	PTGIS	ENST00000478971.1	TSL:1	n.75-8872G>A		intron	N/A
	PTGIS	ENST00000918261.1		c.74+8982G>A		intron	N/A	ENSP00000588320.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38148 AN: 151834 Hom.: 5636 Cov.: 31

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.251 AC: 38152 AN: 151952 Hom.: 5637 Cov.: 31 AF XY: 0.255 AC XY: 18916 AN XY: 74246

African (AFR) AF: 0.114 AC: 4744 AN: 41470

American (AMR) AF: 0.372 AC: 5683 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3468

East Asian (EAS) AF: 0.513 AC: 2648 AN: 5162

South Asian (SAS) AF: 0.300 AC: 1446 AN: 4812

European-Finnish (FIN) AF: 0.269 AC: 2829 AN: 10534

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19103 AN: 67924

Other (OTH) AF: 0.259 AC: 546 AN: 2110

Alfa AF: 0.264 Hom.: 7258

Bravo AF: 0.257

Asia WGS AF: 0.390 AC: 1356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.81
PhyloP100		-0.90
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: rs6125671; hg19: chr20-48175598;