rs13117172

Variant names:

• chr4-23878892-C-T
• rs13117172
• NM_013261.5:c.234+5860G>A

Variant summary

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

The NM_013261.5(PPARGC1A):​c.234+5860G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,044 control chromosomes in the GnomAD database, including 7,070 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 0.27 (7070 hom., cov: 32)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26
• Publications: 7 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=-0.42).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.234+5860G>A		intron_variant	Intron 2 of 12	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.234+5860G>A		intron_variant	Intron 2 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41401 AN: 151926 Hom.: 7063 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.273 AC: 41453 AN: 152044 Hom.: 7070 Cov.: 32 AF XY: 0.274 AC XY: 20390 AN XY: 74322

African (AFR) AF: 0.462 AC: 19148 AN: 41454

American (AMR) AF: 0.286 AC: 4366 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 618 AN: 3468

East Asian (EAS) AF: 0.421 AC: 2168 AN: 5150

South Asian (SAS) AF: 0.340 AC: 1638 AN: 4822

European-Finnish (FIN) AF: 0.163 AC: 1726 AN: 10570

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11100 AN: 67986

Other (OTH) AF: 0.263 AC: 557 AN: 2114

Alfa AF: 0.215 Hom.: 2684

Bravo AF: 0.292

Asia WGS AF: 0.384 AC: 1332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.67
PhyloP100		2.3
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: rs13117172; hg19: chr4-23880515;