19-46621322-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000960.4(PTGIR):​c.1119G>A​(p.Thr373Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,521,222 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 49 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 40 hom. )

Consequence

PTGIR
NM_000960.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.20
Variant links:
Genes affected
PTGIR (HGNC:9602): (prostaglandin I2 receptor) The protein encoded by this gene is a member of the G-protein coupled receptor family 1 and has been shown to be a receptor for prostacyclin. Prostacyclin, the major product of cyclooxygenase in macrovascular endothelium, elicits a potent vasodilation and inhibition of platelet aggregation through binding to this receptor. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 19-46621322-C-T is Benign according to our data. Variant chr19-46621322-C-T is described in ClinVar as [Benign]. Clinvar id is 781491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.2 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0132 (2007/152346) while in subpopulation AFR AF= 0.0442 (1839/41578). AF 95% confidence interval is 0.0425. There are 49 homozygotes in gnomad4. There are 934 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTGIRNM_000960.4 linkc.1119G>A p.Thr373Thr synonymous_variant Exon 3 of 3 ENST00000291294.7 NP_000951.1 P43119

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTGIRENST00000291294.7 linkc.1119G>A p.Thr373Thr synonymous_variant Exon 3 of 3 1 NM_000960.4 ENSP00000291294.1 P43119
PTGIRENST00000598865.5 linkc.483G>A p.Thr161Thr synonymous_variant Exon 3 of 3 3 ENSP00000470799.1 M0QZW0
PTGIRENST00000594275.1 linkc.390G>A p.Thr130Thr synonymous_variant Exon 3 of 3 3 ENSP00000469408.1 M0QXV5
PTGIRENST00000597185.1 linkc.306G>A p.Thr102Thr synonymous_variant Exon 2 of 2 3 ENSP00000470566.1 M0QZI2

Frequencies

GnomAD3 genomes
AF:
0.0131
AC:
1994
AN:
152228
Hom.:
48
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0440
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00765
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.0120
GnomAD3 exomes
AF:
0.00450
AC:
816
AN:
181418
Hom.:
19
AF XY:
0.00348
AC XY:
333
AN XY:
95668
show subpopulations
Gnomad AFR exome
AF:
0.0474
Gnomad AMR exome
AF:
0.00207
Gnomad ASJ exome
AF:
0.00212
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000260
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000171
Gnomad OTH exome
AF:
0.00337
GnomAD4 exome
AF:
0.00140
AC:
1922
AN:
1368876
Hom.:
40
Cov.:
33
AF XY:
0.00127
AC XY:
855
AN XY:
670596
show subpopulations
Gnomad4 AFR exome
AF:
0.0453
Gnomad4 AMR exome
AF:
0.00337
Gnomad4 ASJ exome
AF:
0.00159
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000506
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000158
Gnomad4 OTH exome
AF:
0.00327
GnomAD4 genome
AF:
0.0132
AC:
2007
AN:
152346
Hom.:
49
Cov.:
32
AF XY:
0.0125
AC XY:
934
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.0442
Gnomad4 AMR
AF:
0.00764
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.0118
Alfa
AF:
0.0102
Hom.:
20
Bravo
AF:
0.0153
Asia WGS
AF:
0.00375
AC:
14
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Apr 04, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.50
DANN
Benign
0.63

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.

Other links and lift over

dbSNP: rs2229130; hg19: chr19-47124579; API