NM_013261.5:c.234+10541G>A

Variant names:

• chr4-23874211-C-T
• rs10028665
• NM_013261.5:c.234+10541G>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+10541G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,056 control chromosomes in the GnomAD database, including 4,103 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 0.21 (4103 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• Publications: 3 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=-0.31).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.234+10541G>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+10541G>A		intron_variant	Intron 2 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31308 AN: 151938 Hom.: 4105 Cov.: 33

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0308

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.206 AC: 31304 AN: 152056 Hom.: 4103 Cov.: 33 AF XY: 0.206 AC XY: 15296 AN XY: 74328

African (AFR) AF: 0.0801 AC: 3324 AN: 41500

American (AMR) AF: 0.148 AC: 2256 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3466

East Asian (EAS) AF: 0.0309 AC: 160 AN: 5182

South Asian (SAS) AF: 0.175 AC: 841 AN: 4810

European-Finnish (FIN) AF: 0.347 AC: 3661 AN: 10544

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19618 AN: 67966

Other (OTH) AF: 0.197 AC: 414 AN: 2104

Alfa AF: 0.244 Hom.: 672

Bravo AF: 0.181

Asia WGS AF: 0.121 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.75
PhyloP100		3.2
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: rs10028665; hg19: chr4-23875834;