NM_013261.5:c.234+11064T>C

Variant names:

• chr4-23873688-A-G
• rs6838600
• NM_013261.5:c.234+11064T>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.234+11064T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,040 control chromosomes in the GnomAD database, including 31,134 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 0.64 (31134 hom., cov: 32)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.234+11064T>C		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+11064T>C		intron_variant	Intron 2 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96526 AN: 151922 Hom.: 31145 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.635 AC: 96546 AN: 152040 Hom.: 31134 Cov.: 32 AF XY: 0.633 AC XY: 47057 AN XY: 74308

African (AFR) AF: 0.521 AC: 21599 AN: 41450

American (AMR) AF: 0.585 AC: 8932 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2190 AN: 3472

East Asian (EAS) AF: 0.653 AC: 3374 AN: 5166

South Asian (SAS) AF: 0.674 AC: 3249 AN: 4824

European-Finnish (FIN) AF: 0.692 AC: 7298 AN: 10552

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47762 AN: 67988

Other (OTH) AF: 0.636 AC: 1344 AN: 2114

Alfa AF: 0.678 Hom.: 135408

Bravo AF: 0.621

Asia WGS AF: 0.656 AC: 2282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.76
PhyloP100		0.047
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: rs6838600; hg19: chr4-23875311;