rs5602

Positions:

• chr20-49505441-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000961.4(PTGIS):​c.*2479T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,090 control chromosomes in the GnomAD database, including 31,799 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 0.62 (31793 hom., cov: 32)
  • Exomes 𝑓: 0.50 (6 hom.)
• Consequence: PTGIS NM_000961.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGIS	NM_000961.4	c.*2479T>C		3_prime_UTR_variant	10/10	ENST00000244043.5	NP_000952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGIS	ENST00000244043.5	c.*2479T>C		3_prime_UTR_variant	10/10	1	NM_000961.4	ENSP00000244043	P1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94423 AN: 151920 Hom.: 31735 Cov.: 32

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.659

GnomAD4 exome AF: 0.500 AC: 27 AN: 54 Hom.: 6 Cov.: 0 AF XY: 0.531 AC XY: 17 AN XY: 32

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.700

GnomAD4 genome AF: 0.622 AC: 94531 AN: 152036 Hom.: 31793 Cov.: 32 AF XY: 0.616 AC XY: 45802 AN XY: 74302

Gnomad4 AFR AF: 0.895

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.654

Alfa AF: 0.540 Hom.: 46763

Bravo AF: 0.643

Asia WGS AF: 0.494 AC: 1714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.73

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: rs5602; hg19: chr20-48121978;