3-12350084-G-A

Variant summary

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

The NM_138711.6(PPARG):​c.-8-29620G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,116 control chromosomes in the GnomAD database, including 1,427 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 0.13 ( 1427 hom., cov: 32)

Consequence

PPARG
NM_138711.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0820

Publications

22 publications found
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]
PPARG Gene-Disease associations (from GenCC):
  • PPARG-related familial partial lipodystrophy
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, Genomics England PanelApp
  • Berardinelli-Seip congenital lipodystrophy
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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=-0.82).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPARGNM_138711.6 linkc.-8-29620G>A intron_variant Intron 2 of 7 ENST00000651735.1 NP_619725.3 P37231E9PFV2D2KUA6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPARGENST00000651735.1 linkc.-8-29620G>A intron_variant Intron 2 of 7 NM_138711.6 ENSP00000498313.1 E9PFV2

Frequencies

GnomAD3 genomes
AF:
0.133
AC:
20291
AN:
151998
Hom.:
1422
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.172
Gnomad AMI
AF:
0.0285
Gnomad AMR
AF:
0.101
Gnomad ASJ
AF:
0.0683
Gnomad EAS
AF:
0.0410
Gnomad SAS
AF:
0.129
Gnomad FIN
AF:
0.156
Gnomad MID
AF:
0.0823
Gnomad NFE
AF:
0.127
Gnomad OTH
AF:
0.0985
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.134
AC:
20313
AN:
152116
Hom.:
1427
Cov.:
32
AF XY:
0.134
AC XY:
9936
AN XY:
74360
show subpopulations
African (AFR)
AF:
0.172
AC:
7122
AN:
41492
American (AMR)
AF:
0.101
AC:
1545
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.0683
AC:
237
AN:
3468
East Asian (EAS)
AF:
0.0409
AC:
212
AN:
5180
South Asian (SAS)
AF:
0.130
AC:
626
AN:
4818
European-Finnish (FIN)
AF:
0.156
AC:
1652
AN:
10582
Middle Eastern (MID)
AF:
0.0748
AC:
22
AN:
294
European-Non Finnish (NFE)
AF:
0.127
AC:
8665
AN:
67982
Other (OTH)
AF:
0.0974
AC:
206
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
910
1820
2730
3640
4550
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
224
448
672
896
1120
<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:
0.122
Hom.:
3233
Bravo
AF:
0.131
Asia WGS
AF:
0.0710
AC:
246
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
5.4
DANN
Benign
0.67
PhyloP100
0.082
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs2197423; hg19: chr3-12391583; API