chr20-49510639-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000961.4(PTGIS):​c.1358+389A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,934 control chromosomes in the GnomAD database, including 5,979 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 0.28 ( 5979 hom., cov: 31)

Consequence

PTGIS
NM_000961.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.313

Publications

8 publications found
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 Gene-Disease associations (from GenCC):
  • essential hypertension, genetic
    Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTGISNM_000961.4 linkc.1358+389A>G intron_variant Intron 9 of 9 ENST00000244043.5 NP_000952.1 Q16647

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTGISENST00000244043.5 linkc.1358+389A>G intron_variant Intron 9 of 9 1 NM_000961.4 ENSP00000244043.3 Q16647
PTGISENST00000478971.1 linkn.1179+389A>G intron_variant Intron 8 of 8 1

Frequencies

GnomAD3 genomes
AF:
0.276
AC:
41891
AN:
151816
Hom.:
5973
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.335
Gnomad AMI
AF:
0.149
Gnomad AMR
AF:
0.319
Gnomad ASJ
AF:
0.329
Gnomad EAS
AF:
0.192
Gnomad SAS
AF:
0.267
Gnomad FIN
AF:
0.215
Gnomad MID
AF:
0.347
Gnomad NFE
AF:
0.245
Gnomad OTH
AF:
0.298
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.276
AC:
41925
AN:
151934
Hom.:
5979
Cov.:
31
AF XY:
0.278
AC XY:
20625
AN XY:
74224
show subpopulations
African (AFR)
AF:
0.335
AC:
13885
AN:
41442
American (AMR)
AF:
0.319
AC:
4872
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.329
AC:
1141
AN:
3466
East Asian (EAS)
AF:
0.192
AC:
991
AN:
5172
South Asian (SAS)
AF:
0.269
AC:
1289
AN:
4798
European-Finnish (FIN)
AF:
0.215
AC:
2265
AN:
10538
Middle Eastern (MID)
AF:
0.349
AC:
102
AN:
292
European-Non Finnish (NFE)
AF:
0.245
AC:
16620
AN:
67930
Other (OTH)
AF:
0.296
AC:
624
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1541
3083
4624
6166
7707
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
426
852
1278
1704
2130
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.262
Hom.:
16795
Bravo
AF:
0.284
Asia WGS
AF:
0.232
AC:
804
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
1.5
DANN
Benign
0.42
PhyloP100
-0.31
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs729824; hg19: chr20-48127176; API