chr20-49510639-T-C

Variant names:

• chr20-49510639-T-C
• rs729824
• NM_000961.4:c.1358+389A>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.1358+389A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,934 control chromosomes in the GnomAD database, including 5,979 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 0.28 (5979 hom., cov: 31)
• Consequence: PTGIS NM_000961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• Publications: 8 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 = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGIS	NM_000961.4	c.1358+389A>G		intron_variant	Intron 9 of 9	ENST00000244043.5	NP_000952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGIS	ENST00000244043.5	c.1358+389A>G		intron_variant	Intron 9 of 9	1	NM_000961.4	ENSP00000244043.3
PTGIS	ENST00000478971.1	n.1179+389A>G		intron_variant	Intron 8 of 8	1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41891 AN: 151816 Hom.: 5973 Cov.: 31

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.276 AC: 41925 AN: 151934 Hom.: 5979 Cov.: 31 AF XY: 0.278 AC XY: 20625 AN XY: 74224

African (AFR) AF: 0.335 AC: 13885 AN: 41442

American (AMR) AF: 0.319 AC: 4872 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3466

East Asian (EAS) AF: 0.192 AC: 991 AN: 5172

South Asian (SAS) AF: 0.269 AC: 1289 AN: 4798

European-Finnish (FIN) AF: 0.215 AC: 2265 AN: 10538

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.245 AC: 16620 AN: 67930

Other (OTH) AF: 0.296 AC: 624 AN: 2110

Alfa AF: 0.262 Hom.: 16795

Bravo AF: 0.284

Asia WGS AF: 0.232 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.42
PhyloP100		-0.31
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: rs729824; hg19: chr20-48127176;