chr4-23801584-T-C

Position:

• chr4-23801584-T-C

Variant summary

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

The ENST00000264867.7(PPARGC1A):​c.2293+146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 915,114 control chromosomes in the GnomAD database, including 2,422 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 0.052 (398 hom., cov: 32)
  • Exomes 𝑓: 0.062 (2024 hom.)
• Consequence: PPARGC1A ENST00000264867.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.2293+146A>G		intron_variant		ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.2293+146A>G		intron_variant		1	NM_013261.5	ENSP00000264867	P1
PPARGC1A	ENST00000613098.4	c.1912+146A>G		intron_variant		1		ENSP00000481498
PPARGC1A	ENST00000506055.5	c.*1508+146A>G		intron_variant, NMD_transcript_variant		1		ENSP00000423075
PPARGC1A	ENST00000509702.5	n.2333+146A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0518 AC: 7878 AN: 152176 Hom.: 398 Cov.: 32

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0402

GnomAD4 exome AF: 0.0624 AC: 47575 AN: 762820 Hom.: 2024 AF XY: 0.0611 AC XY: 23628 AN XY: 387012

Gnomad4 AFR exome AF: 0.00821

Gnomad4 AMR exome AF: 0.0186

Gnomad4 ASJ exome AF: 0.0232

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0144

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.0682

Gnomad4 OTH exome AF: 0.0526

GnomAD4 genome AF: 0.0517 AC: 7877 AN: 152294 Hom.: 398 Cov.: 32 AF XY: 0.0554 AC XY: 4126 AN XY: 74454

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.0732

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0651 Hom.: 213

Bravo AF: 0.0369

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.25
DANN	Benign	0.73

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: rs7682765; hg19: chr4-23803207;