rs2932970

Variant names:

• chr4-23817197-G-A
• rs2932970
• NM_013261.5:c.878-2592C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_013261.5(PPARGC1A):​c.878-2592C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,974 control chromosomes in the GnomAD database, including 4,477 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 0.22 (4477 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.878-2592C>T		intron_variant	Intron 7 of 12	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.878-2592C>T		intron_variant	Intron 7 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33714 AN: 151856 Hom.: 4478 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0829

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.222 AC: 33735 AN: 151974 Hom.: 4477 Cov.: 33 AF XY: 0.227 AC XY: 16822 AN XY: 74266

African (AFR) AF: 0.109 AC: 4515 AN: 41456

American (AMR) AF: 0.326 AC: 4975 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3470

East Asian (EAS) AF: 0.0823 AC: 425 AN: 5166

South Asian (SAS) AF: 0.207 AC: 997 AN: 4812

European-Finnish (FIN) AF: 0.336 AC: 3546 AN: 10560

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.263 AC: 17892 AN: 67956

Other (OTH) AF: 0.217 AC: 453 AN: 2092

Alfa AF: 0.259 Hom.: 744

Bravo AF: 0.213

Asia WGS AF: 0.173 AC: 601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Benign	0.77
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2932970; hg19: chr4-23818820;