Variant 4-23884700-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013261.5(PPARGC1A):c.234+52C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,522,370 control chromosomes in the GnomAD database, including 126,848 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 0.41 ( 12875 hom., cov: 33)

Exomes 𝑓: 0.40 ( 113973 hom. )

Consequence

PPARGC1A
NM_013261.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.85

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:

PPARGC1A (HGNC:):

PPARGC1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5 linkuse as main transcript	c.234+52C>A		intron_variant		ENST00000264867.7	NP_037393.1	Q9UBK2-1A0A024R9Q9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7 linkuse as main transcript	c.234+52C>A		intron_variant		1	NM_013261.5	ENSP00000264867.2		Q9UBK2-1

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61551

AN:

151914

Hom.:

12850

Cov.:

show subpopulations

Gnomad AFR

AF:

0.463

Gnomad AMI

AF:

0.403

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.354

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.447

GnomAD3 exomes

AF:

0.367

AC:

80491

AN:

219080

Hom.:

15654

AF XY:

0.373

AC XY:

44078

AN XY:

118046

show subpopulations

Gnomad AFR exome

AF:

0.464

Gnomad AMR exome

AF:

0.209

Gnomad ASJ exome

AF:

0.455

Gnomad EAS exome

AF:

0.373

Gnomad SAS exome

AF:

0.350

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.414

Gnomad OTH exome

AF:

0.392

GnomAD4 exome

AF:

0.405

AC:

554640

AN:

1370338

Hom.:

113973

Cov.:

AF XY:

0.405

AC XY:

274534

AN XY:

678634

show subpopulations

Gnomad4 AFR exome

AF:

0.470

Gnomad4 AMR exome

AF:

0.225

Gnomad4 ASJ exome

AF:

0.455

Gnomad4 EAS exome

AF:

0.364

Gnomad4 SAS exome

AF:

0.358

Gnomad4 FIN exome

AF:

0.268

Gnomad4 NFE exome

AF:

0.419

Gnomad4 OTH exome

AF:

0.416

GnomAD4 genome

AF:

0.405

AC:

61612

AN:

152032

Hom.:

12875

Cov.:

AF XY:

0.397

AC XY:

29489

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.463

Gnomad4 AMR

AF:

0.323

Gnomad4 ASJ

AF:

0.461

Gnomad4 EAS

AF:

0.354

Gnomad4 SAS

AF:

0.342

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.413

Gnomad4 OTH

AF:

0.450

Alfa

AF:

0.409

Hom.:

17795

Bravo

AF:

0.413

Asia WGS

AF:

0.353

AC:

1233

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.14

DANN

Benign

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over