4-23833253-C-A

Position:

• chr4-23833253-C-A

Variant summary

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

The NM_013261.5(PPARGC1A):​c.235-1502G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,034 control chromosomes in the GnomAD database, including 28,012 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 0.61 (28012 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.235-1502G>T		intron_variant		ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.235-1502G>T		intron_variant		1	NM_013261.5	ENSP00000264867	P1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91935 AN: 151916 Hom.: 28004 Cov.: 33

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.605 AC: 91985 AN: 152034 Hom.: 28012 Cov.: 33 AF XY: 0.604 AC XY: 44926 AN XY: 74328

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.624

Alfa AF: 0.623 Hom.: 4227

Bravo AF: 0.607

Asia WGS AF: 0.554 AC: 1926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.60

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: rs4619879; hg19: chr4-23834876;