rs2279525

Positions:

• chr4-23792629-T-C
• chr4-23792629-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013261.5(PPARGC1A):​c.*3193A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,194 control chromosomes in the GnomAD database, including 8,409 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 0.33 (8382 hom., cov: 31)
  • Exomes 𝑓: 0.34 (27 hom.)
• Consequence: PPARGC1A NM_013261.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_013261.5	c.*3193A>G		3_prime_UTR_variant	13/13	ENST00000264867.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.*3193A>G		3_prime_UTR_variant	13/13	1	NM_013261.5	P1
PPARGC1A	ENST00000509702.5	n.2433+3197A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49439 AN: 151644 Hom.: 8363 Cov.: 31

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.336 AC: 145 AN: 432 Hom.: 27 Cov.: 0 AF XY: 0.331 AC XY: 86 AN XY: 260

Gnomad4 FIN exome AF: 0.336

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.326 AC: 49508 AN: 151762 Hom.: 8382 Cov.: 31 AF XY: 0.326 AC XY: 24167 AN XY: 74146

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.310

Alfa AF: 0.287 Hom.: 9901

Bravo AF: 0.322

Asia WGS AF: 0.276 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs2279525; hg19: chr4-23794252;