rs4697429

Positions:

• chr4-23935451-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001330751.2(PPARGC1A):​c.70-50520A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,154 control chromosomes in the GnomAD database, including 3,973 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 0.20 (3973 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.589

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.70-50520A>G		intron_variant			NP_001317680.1
PPARGC1A	NM_001354825.2	c.70-50520A>G		intron_variant			NP_001341754.1
PPARGC1A	NM_001354827.2	c.70-50520A>G		intron_variant			NP_001341756.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30875 AN: 152036 Hom.: 3964 Cov.: 32

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.203 AC: 30891 AN: 152154 Hom.: 3973 Cov.: 32 AF XY: 0.209 AC XY: 15521 AN XY: 74368

Gnomad4 AFR AF: 0.0815

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.191

Alfa AF: 0.217 Hom.: 4725

Bravo AF: 0.209

Asia WGS AF: 0.257 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	5.9
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4697429; hg19: chr4-23937074; COSMIC: COSV67202840;