chr20-49536138-T-C

Variant names:

• chr20-49536138-T-C
• rs6091000
• NM_000961.4:c.673+3432A>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.673+3432A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 152,250 control chromosomes in the GnomAD database, including 682 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 0.081 (682 hom., cov: 33)
• Consequence: PTGIS NM_000961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGIS	NM_000961.4	c.673+3432A>G		intron_variant	Intron 5 of 9	ENST00000244043.5	NP_000952.1
PTGIS	XM_047440325.1	c.673+3432A>G		intron_variant	Intron 5 of 5		XP_047296281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGIS	ENST00000244043.5	c.673+3432A>G		intron_variant	Intron 5 of 9	1	NM_000961.4	ENSP00000244043.3
PTGIS	ENST00000478971.1	n.494+3432A>G		intron_variant	Intron 4 of 8	1

Frequencies

GnomAD3 genomes AF: 0.0811 AC: 12331 AN: 152132 Hom.: 681 Cov.: 33

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0653

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0563

Gnomad OTH AF: 0.0717

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

GnomAD4 genome AF: 0.0811 AC: 12346 AN: 152250 Hom.: 682 Cov.: 33 AF XY: 0.0787 AC XY: 5861 AN XY: 74458

African (AFR) AF: 0.154 AC: 6408 AN: 41524

American (AMR) AF: 0.0431 AC: 659 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 212 AN: 3470

East Asian (EAS) AF: 0.0137 AC: 71 AN: 5184

South Asian (SAS) AF: 0.0591 AC: 285 AN: 4824

European-Finnish (FIN) AF: 0.0653 AC: 693 AN: 10612

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0563 AC: 3832 AN: 68024

Other (OTH) AF: 0.0719 AC: 152 AN: 2114

Alfa AF: 0.0602 Hom.: 604

Bravo AF: 0.0818

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.47
PhyloP100		-1.5
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: rs6091000; hg19: chr20-48152675;