Menu
GeneBe

rs3856806

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_138711.6(PPARG):c.1341C>T(p.His447=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,614,040 control chromosomes in the GnomAD database, including 13,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1153 hom., cov: 32)
Exomes 𝑓: 0.13 ( 12668 hom. )

Consequence

PPARG
NM_138711.6 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.333
Variant links:
Genes affected
PPARG (HGNC:9236): (peroxisome proliferator activated receptor gamma) This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte differentiation. Additionally, PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis and cancer. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 3-12434058-C-T is Benign according to our data. Variant chr3-12434058-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 8139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.333 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPARGNM_138711.6 linkuse as main transcriptc.1341C>T p.His447= synonymous_variant 8/8 ENST00000651735.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPARGENST00000651735.1 linkuse as main transcriptc.1341C>T p.His447= synonymous_variant 8/8 NM_138711.6 P1

Frequencies

GnomAD3 genomes
AF:
0.114
AC:
17378
AN:
152060
Hom.:
1149
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0637
Gnomad AMI
AF:
0.0417
Gnomad AMR
AF:
0.0869
Gnomad ASJ
AF:
0.0712
Gnomad EAS
AF:
0.229
Gnomad SAS
AF:
0.150
Gnomad FIN
AF:
0.200
Gnomad MID
AF:
0.0541
Gnomad NFE
AF:
0.131
Gnomad OTH
AF:
0.0895
GnomAD3 exomes
AF:
0.134
AC:
33702
AN:
251322
Hom.:
2568
AF XY:
0.136
AC XY:
18405
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.0629
Gnomad AMR exome
AF:
0.109
Gnomad ASJ exome
AF:
0.0734
Gnomad EAS exome
AF:
0.241
Gnomad SAS exome
AF:
0.143
Gnomad FIN exome
AF:
0.199
Gnomad NFE exome
AF:
0.126
Gnomad OTH exome
AF:
0.119
GnomAD4 exome
AF:
0.128
AC:
187677
AN:
1461862
Hom.:
12668
Cov.:
32
AF XY:
0.129
AC XY:
93871
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.0572
Gnomad4 AMR exome
AF:
0.107
Gnomad4 ASJ exome
AF:
0.0740
Gnomad4 EAS exome
AF:
0.197
Gnomad4 SAS exome
AF:
0.144
Gnomad4 FIN exome
AF:
0.197
Gnomad4 NFE exome
AF:
0.126
Gnomad4 OTH exome
AF:
0.122
GnomAD4 genome
AF:
0.114
AC:
17390
AN:
152178
Hom.:
1153
Cov.:
32
AF XY:
0.116
AC XY:
8636
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.0638
Gnomad4 AMR
AF:
0.0869
Gnomad4 ASJ
AF:
0.0712
Gnomad4 EAS
AF:
0.229
Gnomad4 SAS
AF:
0.151
Gnomad4 FIN
AF:
0.200
Gnomad4 NFE
AF:
0.131
Gnomad4 OTH
AF:
0.0895
Alfa
AF:
0.120
Hom.:
2734
Bravo
AF:
0.102
Asia WGS
AF:
0.133
AC:
463
AN:
3478
EpiCase
AF:
0.118
EpiControl
AF:
0.114

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxApr 14, 2019This variant is associated with the following publications: (PMID: 18992148, 17141766, 22575725, 21795447, 10851250, 21833536, 9467001) -
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA POLYMORPHISM Benign:1
Benign, no assertion criteria providedliterature onlyOMIMDec 01, 2003- -
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. -
Glioma susceptibility 1 Benign:1
Benign, no assertion criteria providedliterature onlyOMIMJun 01, 2000- -
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
BayesDel_noAF
Benign
-0.43
Cadd
Benign
5.1
Dann
Benign
0.53

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: rs3856806; hg19: chr3-12475557; COSMIC: COSV55140736; API