dbSNP rs2932971: PPARGC1A:c.878-2656G>A (chr4-23817261-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025): 0P and 4B. B1_Strong

The NM_013261.5(PPARGC1A):c.878-2656G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene PPARGC1A is a tumor suppressor gene (CancerMine: 9 TSG citations). The variant allele was found at a cumulative frequency of 0.256 (AC=38,968) in the gnomAD database across 151,964 control chromosomes, including 5,404 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.331. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5404 hom., cov: 32)

Consequence

PPARGC1A
NM_013261.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18

Publications

8 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]

PPARGC1A links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_013261.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 points.

GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.331 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_013261.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPARGC1A	NM_013261.5	MANE Select	c.878-2656G>A	intron	N/A	NP_037393.1	Q9UBK2-1
PPARGC1A	NM_001330751.2		c.893-2656G>A	intron	N/A	NP_001317680.1	Q9UBK2-3
PPARGC1A	NM_001354825.2		c.893-2656G>A	intron	N/A	NP_001341754.1	Q9UBK2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPARGC1A	ENST00000264867.7	TSL:1 MANE Select	c.878-2656G>A	intron	N/A	ENSP00000264867.2	Q9UBK2-1
PPARGC1A	ENST00000613098.4	TSL:1	c.497-2656G>A	intron	N/A	ENSP00000481498.1	Q9UBK2-9
PPARGC1A	ENST00000506055.5	TSL:1	n.*93-2656G>A	intron	N/A	ENSP00000423075.1	Q9UBK2-2

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38919

AN:

151846

Hom.:

5400

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.0822

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.335

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.256

AC:

38968

AN:

151964

Hom.:

5404

Cov.:

AF XY:

0.259

AC XY:

19241

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.229

AC:

9472

AN:

41452

American (AMR)

AF:

0.339

AC:

5164

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

630

AN:

3470

East Asian (EAS)

AF:

0.0817

AC:

421

AN:

5156

South Asian (SAS)

AF:

0.207

AC:

995

AN:

4816

European-Finnish (FIN)

AF:

0.335

AC:

3542

AN:

10570

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.264

AC:

17921

AN:

67946

Other (OTH)

AF:

0.241

AC:

507

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1499

2998

4496

5995

7494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.254

Hom.:

20310

Bravo

AF:

0.253

Asia WGS

AF:

0.182

AC:

633

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.0512

AC:

6286

AN:

122702

Turkish Variome

AF:

0.220

AC:

340

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.0770

AC:

690

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.231

AC:

540

AN:

2342

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over