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GeneBe

rs1801282

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000287820.10(PPARG):c.34C>G(p.Pro12Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0893 in 152022 control chromosomes in the gnomAD Genomes database, including 768 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 768 hom., cov: 32)
Exomes 𝑓: 0.11 ( 1759 hom. )

Consequence

PPARG
ENST00000287820.10 missense

Scores

1
2
15

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.395

Links

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=0.0011972487).
BP6
?
Variant 3-12351626-C-G is Benign according to our data. Variant chr3-12351626-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 130019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPARGNM_138711.6 linkuse as main transcriptc.-8-28078C>G intron_variant ENST00000651735.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPARGENST00000651735.1 linkuse as main transcriptc.-8-28078C>G intron_variant NM_138711.6 P1

Frequencies

GnomAD3 genomes
AF:
0.0893
AC:
13577
AN:
152022
Hom.:
768
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0213
Gnomad AMI
AF:
0.0285
Gnomad AMR
AF:
0.0843
Gnomad ASJ
AF:
0.0577
Gnomad EAS
AF:
0.0406
Gnomad SAS
AF:
0.122
Gnomad FIN
AF:
0.157
Gnomad MID
AF:
0.0633
Gnomad NFE
AF:
0.126
Gnomad OTH
AF:
0.0638
GnomAD3 exomes
AF:
0.110
AC:
27634
AN:
251078
Hom.:
1759
AF XY:
0.111
AC XY:
15096
AN XY:
135690
show subpopulations
Gnomad AFR exome
AF:
0.0201
Gnomad AMR exome
AF:
0.120
Gnomad ASJ exome
AF:
0.0565
Gnomad EAS exome
AF:
0.0383
Gnomad SAS exome
AF:
0.119
Gnomad FIN exome
AF:
0.165
Gnomad NFE exome
AF:
0.124
Gnomad OTH exome
AF:
0.106
GnomAD4 exome
AF:
0.115
AC:
168301
AN:
1457372
Hom.:
10627
AF XY:
0.117
AC XY:
84648
AN XY:
725298
show subpopulations
Gnomad4 AFR exome
AF:
0.0154
Gnomad4 AMR exome
AF:
0.118
Gnomad4 ASJ exome
AF:
0.0562
Gnomad4 EAS exome
AF:
0.0360
Gnomad4 SAS exome
AF:
0.123
Gnomad4 FIN exome
AF:
0.170
Gnomad4 NFE exome
AF:
0.121
Gnomad4 OTH exome
AF:
0.101
Alfa
AF:
0.105
Hom.:
722
Bravo
AF:
0.0805
TwinsUK
AF:
0.108
AC:
401
ALSPAC
AF:
0.119
AC:
460
ESP6500AA
AF:
0.0261
AC:
115
ESP6500EA
AF:
0.124
AC:
1063
ExAC
AF:
0.110
AC:
13366
Asia WGS
AF:
0.0570
AC:
199
AN:
3478
EpiCase
AF:
0.112
EpiControl
AF:
0.108

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxJun 09, 2021This variant is associated with the following publications: (PMID: 26049557, 26025336, 26273662, 25216344, 24319532, 23300871, 22800638, 24141935, 23633103, 28386678, 29632382, 28924543, 24447396, 11289055, 26551672, 23666678, 27398621, 11289057, 9792554, 21155004, 25157153, 22276212, 20591056, 17495181, 20930717, 9806549, 10973253, 10873398, 21833536, 20450366, 22378291, 10851250, 21795447, 20623456, 22575725, 19465486, 20368233, 21508507, 20424228, 12974743, 19178525, 22168210, 17187763, 22958899, 23161442) -
Benign, criteria provided, single submitterclinical testingInvitaeNov 01, 2022- -
not specified Benign:1
Likely benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of Chicago-Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Obesity Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Diabetes Mellitus, Noninsulin-Dependent, with Acanthosis Nigricans and Hypertension Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
PPARG-related familial partial lipodystrophy Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.053
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.23
Cadd
Benign
15
Dann
Uncertain
0.98
DEOGEN2
Benign
0.26
T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.54
D
LIST_S2
Benign
0.72
T
MetaRNN
Benign
0.0012
T
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
0.96
P;P;P;P;P;P;P;P
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.050
N
REVEL
Benign
0.24
Sift
Uncertain
0.015
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.0
B
Vest4
0.075
MPC
0.12
ClinPred
0.019
T
GERP RS
2.9
Varity_R
0.075
gMVP
0.24

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: rs1801282; hg19: chr3-12393125; COSMIC: COSV55140710; API