Variant chr20-49524145-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000961.4(PTGIS):c.768G>A(p.Leu256=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0695 in 1,614,182 control chromosomes in the GnomAD database, including 4,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.095 ( 854 hom., cov: 33)

Exomes 𝑓: 0.067 ( 3735 hom. )

Consequence

PTGIS
NM_000961.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.68

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 20-49524145-C-T is Benign according to our data. Variant chr20-49524145-C-T is described in ClinVar as [Benign]. Clinvar id is 3056980.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGIS	NM_000961.4 linkuse as main transcript	c.768G>A	p.Leu256=	synonymous_variant	6/10	ENST00000244043.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGIS	ENST00000244043.5 linkuse as main transcript	c.768G>A	p.Leu256=	synonymous_variant	6/10	1	NM_000961.4	P1
PTGIS	ENST00000478971.1 linkuse as main transcript	n.589G>A		non_coding_transcript_exon_variant	5/9	1

Frequencies

GnomAD3 genomes

AF:

0.0955

AC:

14527

AN:

152180

Hom.:

852

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.0749

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.0504

Gnomad EAS

AF:

0.0892

Gnomad SAS

AF:

0.0978

Gnomad FIN

AF:

0.0750

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0612

Gnomad OTH

AF:

0.0759

GnomAD3 exomes

AF:

0.0823

AC:

20685

AN:

251420

Hom.:

963

AF XY:

0.0792

AC XY:

10763

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.0484

Gnomad EAS exome

AF:

0.0960

Gnomad SAS exome

AF:

0.0890

Gnomad FIN exome

AF:

0.0785

Gnomad NFE exome

AF:

0.0595

Gnomad OTH exome

AF:

0.0771

GnomAD4 exome

AF:

0.0668

AC:

97624

AN:

1461884

Hom.:

3735

Cov.:

AF XY:

0.0670

AC XY:

48707

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.0452

Gnomad4 EAS exome

AF:

0.0777

Gnomad4 SAS exome

AF:

0.0864

Gnomad4 FIN exome

AF:

0.0775

Gnomad4 NFE exome

AF:

0.0593

Gnomad4 OTH exome

AF:

0.0746

GnomAD4 genome

AF:

0.0955

AC:

14544

AN:

152298

Hom.:

854

Cov.:

AF XY:

0.0966

AC XY:

7190

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.0504

Gnomad4 EAS

AF:

0.0894

Gnomad4 SAS

AF:

0.0966

Gnomad4 FIN

AF:

0.0750

Gnomad4 NFE

AF:

0.0612

Gnomad4 OTH

AF:

0.0761

Alfa

AF:

0.0690

Hom.:

747

Bravo

AF:

0.101

Asia WGS

AF:

0.105

AC:

365

AN:

3478

EpiCase

AF:

0.0636

EpiControl

AF:

0.0640

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PTGIS-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.0

DANN

Benign

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over