20-49561247-G-A

Variant names:

• chr20-49561247-G-A
• rs476496
• NM_000961.4:c.74+6796C>T

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+6796C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,010 control chromosomes in the GnomAD database, including 45,665 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 0.77 (45665 hom., cov: 31)
• Consequence: PTGIS NM_000961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 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.74+6796C>T		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.74+6796C>T		intron	N/A	ENSP00000244043.3
	PTGIS	ENST00000478971.1	TSL:1	n.74+6796C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117097 AN: 151892 Hom.: 45618 Cov.: 31

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.771 AC: 117195 AN: 152010 Hom.: 45665 Cov.: 31 AF XY: 0.768 AC XY: 57054 AN XY: 74280

African (AFR) AF: 0.869 AC: 36060 AN: 41478

American (AMR) AF: 0.675 AC: 10298 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1852 AN: 3462

East Asian (EAS) AF: 0.636 AC: 3280 AN: 5154

South Asian (SAS) AF: 0.716 AC: 3439 AN: 4806

European-Finnish (FIN) AF: 0.807 AC: 8534 AN: 10578

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51309 AN: 67954

Other (OTH) AF: 0.720 AC: 1523 AN: 2114

Alfa AF: 0.743 Hom.: 103420

Bravo AF: 0.760

Asia WGS AF: 0.699 AC: 2431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.13
DANN	Benign	0.19
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: rs476496; hg19: chr20-48177784;