chr20-49517245-G-A

Variant names:

• chr20-49517245-G-A
• rs6090996
• NM_000961.4:c.856-2850C>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.856-2850C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,146 control chromosomes in the GnomAD database, including 5,384 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 (5384 hom., cov: 32)
• Consequence: PTGIS NM_000961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGIS	NM_000961.4	c.856-2850C>T		intron_variant	Intron 6 of 9	ENST00000244043.5	NP_000952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGIS	ENST00000244043.5	c.856-2850C>T		intron_variant	Intron 6 of 9	1	NM_000961.4	ENSP00000244043.3
PTGIS	ENST00000478971.1	n.677-2850C>T		intron_variant	Intron 5 of 8	1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37868 AN: 152028 Hom.: 5371 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0946

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.249 AC: 37923 AN: 152146 Hom.: 5384 Cov.: 32 AF XY: 0.243 AC XY: 18106 AN XY: 74378

African (AFR) AF: 0.393 AC: 16296 AN: 41492

American (AMR) AF: 0.230 AC: 3513 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 768 AN: 3470

East Asian (EAS) AF: 0.0944 AC: 488 AN: 5170

South Asian (SAS) AF: 0.212 AC: 1023 AN: 4824

European-Finnish (FIN) AF: 0.134 AC: 1415 AN: 10592

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13550 AN: 67984

Other (OTH) AF: 0.270 AC: 572 AN: 2116

Alfa AF: 0.205 Hom.: 3477

Bravo AF: 0.262

Asia WGS AF: 0.180 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.54
PhyloP100		0.51
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: rs6090996; hg19: chr20-48133782;