4-24055643-C-T

Variant names:

• chr4-24055643-C-T
• rs590183
• NM_001330751.2:c.69+35825G>A

Variant summary

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

The NM_001330751.2(PPARGC1A):​c.69+35825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,094 control chromosomes in the GnomAD database, including 11,667 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 0.39 (11667 hom., cov: 33)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.69+35825G>A		intron_variant	Intron 3 of 14		NP_001317680.1
PPARGC1A	NM_001354825.2	c.69+35825G>A		intron_variant	Intron 2 of 13		NP_001341754.1
PPARGC1A	NM_001354827.2	c.69+35825G>A		intron_variant	Intron 2 of 13		NP_001341756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59226 AN: 151976 Hom.: 11662 Cov.: 33

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.390 AC: 59257 AN: 152094 Hom.: 11667 Cov.: 33 AF XY: 0.388 AC XY: 28892 AN XY: 74394

African (AFR) AF: 0.356 AC: 14752 AN: 41460

American (AMR) AF: 0.396 AC: 6063 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1458 AN: 3470

East Asian (EAS) AF: 0.401 AC: 2072 AN: 5166

South Asian (SAS) AF: 0.437 AC: 2107 AN: 4822

European-Finnish (FIN) AF: 0.352 AC: 3725 AN: 10580

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.408 AC: 27746 AN: 67986

Other (OTH) AF: 0.413 AC: 873 AN: 2112

Alfa AF: 0.379 Hom.: 6009

Bravo AF: 0.392

Asia WGS AF: 0.417 AC: 1453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.69
PhyloP100		-0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs590183; hg19: chr4-24057266;