5-149832947-C-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_133263.4(PPARGC1B):c.874C>A(p.Arg292Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0426 in 1,613,134 control chromosomes in the GnomAD database, including 2,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.076 ( 748 hom., cov: 32)
Exomes 𝑓: 0.039 ( 1798 hom. )
Consequence
PPARGC1B
NM_133263.4 missense
NM_133263.4 missense
Scores
3
3
10
Clinical Significance
Conservation
PhyloP100: 4.86
Genes affected
PPARGC1B (HGNC:30022): (PPARG coactivator 1 beta) The protein encoded by this gene stimulates the activity of several transcription factors and nuclear receptors, including estrogen receptor alpha, nuclear respiratory factor 1, and glucocorticoid receptor. The encoded protein may be involved in fat oxidation, non-oxidative glucose metabolism, and the regulation of energy expenditure. This protein is downregulated in prediabetic and type 2 diabetes mellitus patients. Certain allelic variations in this gene increase the risk of the development of obesity. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0016933084).
BP6
?
Variant 5-149832947-C-A is Benign according to our data. Variant chr5-149832947-C-A is described in ClinVar as [Benign]. Clinvar id is 1288654.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPARGC1B | NM_133263.4 | c.874C>A | p.Arg292Ser | missense_variant | 5/12 | ENST00000309241.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPARGC1B | ENST00000309241.10 | c.874C>A | p.Arg292Ser | missense_variant | 5/12 | 1 | NM_133263.4 | P2 | |
PPARGC1B | ENST00000394320.7 | c.874C>A | p.Arg292Ser | missense_variant | 5/11 | 1 | A2 | ||
PPARGC1B | ENST00000360453.8 | c.757C>A | p.Arg253Ser | missense_variant | 4/11 | 1 | A2 | ||
PPARGC1B | ENST00000403750.5 | c.682C>A | p.Arg228Ser | missense_variant | 4/11 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0758 AC: 11529AN: 152090Hom.: 746 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0507 AC: 12600AN: 248750Hom.: 592 AF XY: 0.0494 AC XY: 6662AN XY: 134986
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GnomAD4 exome AF: 0.0391 AC: 57194AN: 1460926Hom.: 1798 Cov.: 32 AF XY: 0.0396 AC XY: 28799AN XY: 726744
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GnomAD4 genome ? AF: 0.0758 AC: 11535AN: 152208Hom.: 748 Cov.: 32 AF XY: 0.0746 AC XY: 5554AN XY: 74430
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98
ESP6500AA
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776
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292
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6588
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337
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Pathogenic
D;D;D;D
Sift4G
Benign
T;T;D;T
Polyphen
D;D;D;.
Vest4
MPC
0.69
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at