rs2290603

Variant names:

• chr4-23824810-A-G
• rs2290603
• NM_013261.5:c.758-302T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013261.5(PPARGC1A):​c.758-302T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,104 control chromosomes in the GnomAD database, including 51,347 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 0.82 (51347 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.758-302T>C		intron_variant	Intron 5 of 12	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.758-302T>C		intron_variant	Intron 5 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124637 AN: 151986 Hom.: 51290 Cov.: 33

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.820 AC: 124753 AN: 152104 Hom.: 51347 Cov.: 33 AF XY: 0.823 AC XY: 61220 AN XY: 74346

African (AFR) AF: 0.878 AC: 36467 AN: 41530

American (AMR) AF: 0.859 AC: 13102 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2946 AN: 3470

East Asian (EAS) AF: 0.775 AC: 3997 AN: 5156

South Asian (SAS) AF: 0.837 AC: 4038 AN: 4824

European-Finnish (FIN) AF: 0.815 AC: 8639 AN: 10596

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52868 AN: 67952

Other (OTH) AF: 0.836 AC: 1768 AN: 2116

Alfa AF: 0.808 Hom.: 15617

Bravo AF: 0.825

Asia WGS AF: 0.848 AC: 2949 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		-0.65
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: rs2290603; hg19: chr4-23826433;