rs16874194

Positions:

• chr4-23825764-T-C

Variant summary

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

The NM_013261.5(PPARGC1A):​c.758-1256A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 152,186 control chromosomes in the GnomAD database, including 768 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 0.098 (768 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

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=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_013261.5	c.758-1256A>G		intron_variant		ENST00000264867.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.758-1256A>G		intron_variant		1	NM_013261.5	P1

Frequencies

GnomAD3 genomes AF: 0.0977 AC: 14862 AN: 152068 Hom.: 769 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0977 AC: 14871 AN: 152186 Hom.: 768 Cov.: 33 AF XY: 0.103 AC XY: 7631 AN XY: 74406

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0983

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0790 Hom.: 118

Bravo AF: 0.0942

Asia WGS AF: 0.146 AC: 506 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.7
DANN	Benign	0.84

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: rs16874194; hg19: chr4-23827387;