Variant chr20-49513169-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_000961.4(PTGIS):c.1117C>A(p.Arg373=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,613,868 control chromosomes in the GnomAD database, including 48,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.22 ( 3965 hom., cov: 31)

Exomes 𝑓: 0.24 ( 44655 hom. )

Consequence

PTGIS
NM_000961.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.45

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 20-49513169-G-T is Benign according to our data. Variant chr20-49513169-G-T is described in ClinVar as [Benign]. Clinvar id is 3060885.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.45 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.296 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.1117C>A	p.Arg373=	synonymous_variant	8/10	ENST00000244043.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGIS	ENST00000244043.5 linkuse as main transcript	c.1117C>A	p.Arg373=	synonymous_variant	8/10	1	NM_000961.4	P1
PTGIS	ENST00000478971.1 linkuse as main transcript	n.938C>A		non_coding_transcript_exon_variant	7/9	1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33454

AN:

151912

Hom.:

3966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.327

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.275

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.267

GnomAD3 exomes

AF:

0.253

AC:

63525

AN:

251076

Hom.:

8410

AF XY:

0.257

AC XY:

34933

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.313

Gnomad ASJ exome

AF:

0.343

Gnomad EAS exome

AF:

0.220

Gnomad SAS exome

AF:

0.285

Gnomad FIN exome

AF:

0.207

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.244

AC:

356948

AN:

1461836

Hom.:

44655

Cov.:

AF XY:

0.246

AC XY:

179006

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.308

Gnomad4 ASJ exome

AF:

0.347

Gnomad4 EAS exome

AF:

0.224

Gnomad4 SAS exome

AF:

0.285

Gnomad4 FIN exome

AF:

0.211

Gnomad4 NFE exome

AF:

0.240

Gnomad4 OTH exome

AF:

0.260

GnomAD4 genome

AF:

0.220

AC:

33456

AN:

152032

Hom.:

3965

Cov.:

AF XY:

0.224

AC XY:

16668

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.303

Gnomad4 ASJ

AF:

0.327

Gnomad4 EAS

AF:

0.227

Gnomad4 SAS

AF:

0.277

Gnomad4 FIN

AF:

0.215

Gnomad4 NFE

AF:

0.243

Gnomad4 OTH

AF:

0.265

Alfa

AF:

0.232

Hom.:

5113

Bravo

AF:

0.221

Asia WGS

AF:

0.250

AC:

866

AN:

3478

EpiCase

AF:

0.263

EpiControl

AF:

0.263

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

-0.36

CADD

Benign

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