rs6019902

Positions:

• chr20-49561676-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PTGIS	NM_000961.4	c.74+6367C>T		intron_variant		ENST00000244043.5
PTGIS	XM_047440325.1	c.74+6367C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGIS	ENST00000244043.5	c.74+6367C>T		intron_variant		1	NM_000961.4	P1
PTGIS	ENST00000478971.1	n.74+6367C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.0724

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.203

Alfa AF: 0.187 Hom.: 2727

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6019902; hg19: chr20-48178213;