4-23864393-C-T

Variant summary

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

The NM_013261.5(PPARGC1A):​c.234+20359G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,208 control chromosomes in the GnomAD database, including 47,115 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 0.78 ( 47115 hom., cov: 33)

Consequence

PPARGC1A
NM_013261.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

18 publications found
Variant links:
Genes affected
PPARGC1A (HGNC:9237): (PPARG coactivator 1 alpha) The protein encoded by this gene is a transcriptional coactivator that regulates the genes involved in energy metabolism. This protein interacts with PPARgamma, which permits the interaction of this protein with multiple transcription factors. This protein can interact with, and regulate the activities of, cAMP response element binding protein (CREB) and nuclear respiratory factors (NRFs). It provides a direct link between external physiological stimuli and the regulation of mitochondrial biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity. [provided by RefSeq, Jul 2008]

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=-0.86).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPARGC1ANM_013261.5 linkc.234+20359G>A intron_variant Intron 2 of 12 ENST00000264867.7 NP_037393.1 Q9UBK2-1A0A024R9Q9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPARGC1AENST00000264867.7 linkc.234+20359G>A intron_variant Intron 2 of 12 1 NM_013261.5 ENSP00000264867.2 Q9UBK2-1

Frequencies

GnomAD3 genomes
AF:
0.783
AC:
119118
AN:
152090
Hom.:
47049
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.891
Gnomad AMI
AF:
0.871
Gnomad AMR
AF:
0.711
Gnomad ASJ
AF:
0.752
Gnomad EAS
AF:
0.632
Gnomad SAS
AF:
0.669
Gnomad FIN
AF:
0.833
Gnomad MID
AF:
0.715
Gnomad NFE
AF:
0.747
Gnomad OTH
AF:
0.757
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.783
AC:
119246
AN:
152208
Hom.:
47115
Cov.:
33
AF XY:
0.785
AC XY:
58434
AN XY:
74410
show subpopulations
African (AFR)
AF:
0.891
AC:
37019
AN:
41544
American (AMR)
AF:
0.711
AC:
10871
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.752
AC:
2608
AN:
3470
East Asian (EAS)
AF:
0.633
AC:
3261
AN:
5150
South Asian (SAS)
AF:
0.670
AC:
3232
AN:
4824
European-Finnish (FIN)
AF:
0.833
AC:
8831
AN:
10600
Middle Eastern (MID)
AF:
0.721
AC:
212
AN:
294
European-Non Finnish (NFE)
AF:
0.747
AC:
50814
AN:
68014
Other (OTH)
AF:
0.760
AC:
1604
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1339
2677
4016
5354
6693
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
864
1728
2592
3456
4320
<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:
0.751
Hom.:
187963
Bravo
AF:
0.779
Asia WGS
AF:
0.680
AC:
2367
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
4.2
DANN
Benign
0.62
PhyloP100
0.23
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: rs7656250; hg19: chr4-23866016; API