20-49522434-T-C

Variant names:

• chr20-49522434-T-C
• rs508757
• NM_000961.4:c.855+1624A>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.855+1624A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,624 control chromosomes in the GnomAD database, including 9,800 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 0.31 (9800 hom., cov: 30)
• Consequence: PTGIS NM_000961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGIS	NM_000961.4	c.855+1624A>G		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.855+1624A>G		intron_variant	Intron 6 of 9	1	NM_000961.4	ENSP00000244043.3
PTGIS	ENST00000478971.1	n.676+1624A>G		intron_variant	Intron 5 of 8	1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47072 AN: 151506 Hom.: 9764 Cov.: 30

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0691

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.311 AC: 47162 AN: 151624 Hom.: 9800 Cov.: 30 AF XY: 0.304 AC XY: 22492 AN XY: 74094

African (AFR) AF: 0.602 AC: 24822 AN: 41232

American (AMR) AF: 0.230 AC: 3505 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 666 AN: 3464

East Asian (EAS) AF: 0.0696 AC: 358 AN: 5140

South Asian (SAS) AF: 0.224 AC: 1074 AN: 4790

European-Finnish (FIN) AF: 0.172 AC: 1817 AN: 10550

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.206 AC: 13999 AN: 67912

Other (OTH) AF: 0.290 AC: 610 AN: 2100

Alfa AF: 0.226 Hom.: 8834

Bravo AF: 0.328

Asia WGS AF: 0.192 AC: 669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.45
PhyloP100		-0.30
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: rs508757; hg19: chr20-48138971;