rs4235308

Variant names:

• chr4-23862789-T-C
• rs4235308
• NM_013261.5:c.234+21963A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-23862789-T-C
• chr4-23862789-T-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.234+21963A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,036 control chromosomes in the GnomAD database, including 12,183 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 0.40 (12183 hom., cov: 32)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.234+21963A>G		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+21963A>G		intron_variant	Intron 2 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60740 AN: 151918 Hom.: 12155 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.400 AC: 60807 AN: 152036 Hom.: 12183 Cov.: 32 AF XY: 0.401 AC XY: 29765 AN XY: 74314

African (AFR) AF: 0.374 AC: 15527 AN: 41470

American (AMR) AF: 0.392 AC: 5988 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1661 AN: 3470

East Asian (EAS) AF: 0.436 AC: 2247 AN: 5156

South Asian (SAS) AF: 0.445 AC: 2140 AN: 4814

European-Finnish (FIN) AF: 0.381 AC: 4027 AN: 10570

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.406 AC: 27604 AN: 67966

Other (OTH) AF: 0.414 AC: 875 AN: 2114

Alfa AF: 0.405 Hom.: 52778

Bravo AF: 0.398

Asia WGS AF: 0.465 AC: 1618 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.071
DANN	Benign	0.47
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: rs4235308; hg19: chr4-23864412;