4-23994752-G-A

Position:

• chr4-23994752-G-A

Variant summary

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

The NM_001330751.2(PPARGC1A):​c.69+96716C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,078 control chromosomes in the GnomAD database, including 2,794 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 0.17 (2794 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.69+96716C>T		intron_variant			NP_001317680.1
PPARGC1A	NM_001354825.2	c.69+96716C>T		intron_variant			NP_001341754.1
PPARGC1A	NM_001354827.2	c.69+96716C>T		intron_variant			NP_001341756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26419 AN: 151960 Hom.: 2791 Cov.: 32

Gnomad AFR AF: 0.0850

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.174 AC: 26438 AN: 152078 Hom.: 2794 Cov.: 32 AF XY: 0.180 AC XY: 13386 AN XY: 74332

Gnomad4 AFR AF: 0.0849

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.164

Alfa AF: 0.184 Hom.: 3679

Bravo AF: 0.175

Asia WGS AF: 0.243 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16874509; hg19: chr4-23996375;