4-23864393-C-T

Variant names:

• chr4-23864393-C-T
• rs7656250
• NM_013261.5:c.234+20359G>A

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+20359G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,208 control chromosomes in the GnomAD database, including 47,115 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 0.78 (47115 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 18 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.234+20359G>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+20359G>A		intron_variant	Intron 2 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119118 AN: 152090 Hom.: 47049 Cov.: 33

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.783 AC: 119246 AN: 152208 Hom.: 47115 Cov.: 33 AF XY: 0.785 AC XY: 58434 AN XY: 74410

African (AFR) AF: 0.891 AC: 37019 AN: 41544

American (AMR) AF: 0.711 AC: 10871 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2608 AN: 3470

East Asian (EAS) AF: 0.633 AC: 3261 AN: 5150

South Asian (SAS) AF: 0.670 AC: 3232 AN: 4824

European-Finnish (FIN) AF: 0.833 AC: 8831 AN: 10600

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.747 AC: 50814 AN: 68014

Other (OTH) AF: 0.760 AC: 1604 AN: 2110

Alfa AF: 0.751 Hom.: 187963

Bravo AF: 0.779

Asia WGS AF: 0.680 AC: 2367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.62
PhyloP100		0.23
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: rs7656250; hg19: chr4-23866016;