rs4383605

chr4-23893586-T-G

Variant summary

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

The NM_001330751.2(PPARGC1A):c.70-8655A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,092 control chromosomes in the GnomAD database, including 4,731 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 0.22 (4731 hom., cov: 33)
• Consequence: PPARGC1A NM_001330751.2 intron
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_001330751.2	c.70-8655A>C		intron_variant
PPARGC1A	NM_001330752.2	c.19-8655A>C		intron_variant
PPARGC1A	NM_001354825.2	c.70-8655A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1A	ENST00000507342.5	n.53-3373A>C		intron_variant, non_coding_transcript_variant		3
PPARGC1A	ENST00000514494.1	n.97-8655A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32930 AN: 151976 Hom.: 4731 Cov.: 33

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0302

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.216 AC: 32926 AN: 152092 Hom.: 4731 Cov.: 33 AF XY: 0.216 AC XY: 16031 AN XY: 74384

Gnomad4 AFR AF: 0.0559

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.0301

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.210

Alfa AF: 0.266 Hom.: 831

Bravo AF: 0.191

Asia WGS AF: 0.126 AC: 436 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	18
Dann	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4383605; hg19: chr4-23895209;