rs6019902

Variant names:

• chr20-49561676-G-A
• rs6019902
• NM_000961.4:c.74+6367C>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+6367C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,084 control chromosomes in the GnomAD database, including 3,288 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 0.20 (3288 hom., cov: 32)
• Consequence: PTGIS NM_000961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.793
• 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGIS	NM_000961.4	c.74+6367C>T		intron_variant	Intron 1 of 9	ENST00000244043.5	NP_000952.1
PTGIS	XM_047440325.1	c.74+6367C>T		intron_variant	Intron 1 of 5		XP_047296281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGIS	ENST00000244043.5	c.74+6367C>T		intron_variant	Intron 1 of 9	1	NM_000961.4	ENSP00000244043.3
PTGIS	ENST00000478971.1	n.74+6367C>T		intron_variant	Intron 1 of 8	1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30926 AN: 151966 Hom.: 3280 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0734

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.204 AC: 30961 AN: 152084 Hom.: 3288 Cov.: 32 AF XY: 0.202 AC XY: 15009 AN XY: 74362

African (AFR) AF: 0.254 AC: 10542 AN: 41460

American (AMR) AF: 0.214 AC: 3266 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 500 AN: 3466

East Asian (EAS) AF: 0.149 AC: 773 AN: 5180

South Asian (SAS) AF: 0.0724 AC: 349 AN: 4818

European-Finnish (FIN) AF: 0.218 AC: 2307 AN: 10568

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12559 AN: 67998

Other (OTH) AF: 0.203 AC: 429 AN: 2110

Alfa AF: 0.190 Hom.: 3500

Bravo AF: 0.208

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.1
DANN	Benign	0.87
PhyloP100		0.79
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: rs6019902; hg19: chr20-48178213;