20-49526825-T-C

Position:

• chr20-49526825-T-C

Variant summary

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

The NM_000961.4(PTGIS):​c.674-2586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 152,086 control chromosomes in the GnomAD database, including 29,954 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 0.61 (29954 hom., cov: 32)
• Consequence: PTGIS NM_000961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGIS	NM_000961.4	c.674-2586A>G		intron_variant		ENST00000244043.5	NP_000952.1
PTGIS	XM_047440325.1	c.*3216A>G		3_prime_UTR_variant	6/6		XP_047296281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGIS	ENST00000244043.5	c.674-2586A>G		intron_variant		1	NM_000961.4	ENSP00000244043	P1
PTGIS	ENST00000478971.1	n.495-2586A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 92010 AN: 151968 Hom.: 29898 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.606 AC: 92129 AN: 152086 Hom.: 29954 Cov.: 32 AF XY: 0.601 AC XY: 44679 AN XY: 74312

Gnomad4 AFR AF: 0.851

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.624

Alfa AF: 0.540 Hom.: 31640

Bravo AF: 0.613

Asia WGS AF: 0.452 AC: 1576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.47
DANN	Benign	0.37

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: rs522962; hg19: chr20-48143362;