chr4-23825764-T-C

Variant names:

• chr4-23825764-T-C
• rs16874194
• NM_013261.5:c.758-1256A>G

Variant summary

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

The NM_013261.5(PPARGC1A):​c.758-1256A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 152,186 control chromosomes in the GnomAD database, including 768 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 0.098 (768 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• 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=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.758-1256A>G		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.758-1256A>G		intron_variant	Intron 5 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.0977 AC: 14862 AN: 152068 Hom.: 769 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0977 AC: 14871 AN: 152186 Hom.: 768 Cov.: 33 AF XY: 0.103 AC XY: 7631 AN XY: 74406

African (AFR) AF: 0.108 AC: 4502 AN: 41550

American (AMR) AF: 0.105 AC: 1598 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 341 AN: 3468

East Asian (EAS) AF: 0.192 AC: 992 AN: 5160

South Asian (SAS) AF: 0.143 AC: 690 AN: 4828

European-Finnish (FIN) AF: 0.128 AC: 1360 AN: 10598

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.0740 AC: 5034 AN: 68000

Other (OTH) AF: 0.100 AC: 212 AN: 2114

Alfa AF: 0.0808 Hom.: 142

Bravo AF: 0.0942

Asia WGS AF: 0.146 AC: 506 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.7
DANN	Benign	0.84
PhyloP100		1.3
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: rs16874194; hg19: chr4-23827387;