rs2970870

Positions:

• chr4-23891394-A-G

Variant summary

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

The NM_001330751.2(PPARGC1A):​c.70-6463T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,044 control chromosomes in the GnomAD database, including 19,208 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 0.48 (19208 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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]

PPARGC1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.70-6463T>C		intron_variant			NP_001317680.1
PPARGC1A	NM_001354825.2	c.70-6463T>C		intron_variant			NP_001341754.1
PPARGC1A	NM_001354827.2	c.70-6463T>C		intron_variant			NP_001341756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000507342.5	n.53-1181T>C		intron_variant		3
PPARGC1A	ENST00000514494.1	n.97-6463T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73608 AN: 151926 Hom.: 19191 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.484 AC: 73656 AN: 152044 Hom.: 19208 Cov.: 32 AF XY: 0.481 AC XY: 35714 AN XY: 74296

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.488

Alfa AF: 0.429 Hom.: 23724

Bravo AF: 0.495

Asia WGS AF: 0.485 AC: 1687 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.8
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2970870; hg19: chr4-23893017;