rs10018239

chr4-23853268-A-Gchr4-23853268-A-T

Variant summary

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

The NM_013261.5(PPARGC1A):c.235-21517T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,008 control chromosomes in the GnomAD database, including 12,765 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 0.40 (12765 hom., cov: 32)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_013261.5	c.235-21517T>C		intron_variant		ENST00000264867.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.235-21517T>C		intron_variant		1	NM_013261.5	P1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60080 AN: 151890 Hom.: 12756 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.396 AC: 60130 AN: 152008 Hom.: 12765 Cov.: 32 AF XY: 0.393 AC XY: 29187 AN XY: 74294

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.358

Alfa AF: 0.395 Hom.: 1487

Bravo AF: 0.387

Asia WGS AF: 0.229 AC: 796 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	3.1
Dann	Benign	0.62

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: rs10018239; hg19: chr4-23854891;