4-24053802-T-G

Variant names:

• chr4-24053802-T-G
• rs614457
• NM_001330751.2:c.69+37666A>C

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+37666A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 151,940 control chromosomes in the GnomAD database, including 29,529 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 0.62 (29529 hom., cov: 31)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479
• Publications: 2 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 (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.69+37666A>C		intron_variant	Intron 3 of 14		NP_001317680.1
PPARGC1A	NM_001354825.2	c.69+37666A>C		intron_variant	Intron 2 of 13		NP_001341754.1
PPARGC1A	NM_001354827.2	c.69+37666A>C		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: 0.622 AC: 94416 AN: 151820 Hom.: 29507 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.622 AC: 94486 AN: 151940 Hom.: 29529 Cov.: 31 AF XY: 0.618 AC XY: 45894 AN XY: 74260

African (AFR) AF: 0.629 AC: 26058 AN: 41424

American (AMR) AF: 0.562 AC: 8581 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2205 AN: 3466

East Asian (EAS) AF: 0.512 AC: 2640 AN: 5158

South Asian (SAS) AF: 0.588 AC: 2822 AN: 4800

European-Finnish (FIN) AF: 0.633 AC: 6685 AN: 10562

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43607 AN: 67934

Other (OTH) AF: 0.626 AC: 1322 AN: 2112

Alfa AF: 0.631 Hom.: 15086

Bravo AF: 0.615

Asia WGS AF: 0.552 AC: 1922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.57
PhyloP100		0.48

Splicing

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

Other links and lift over

dbSNP: rs614457; hg19: chr4-24055425;