4-24047189-G-T

Variant names:

• chr4-24047189-G-T
• rs16874778
• NM_001330751.2:c.69+44279C>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+44279C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,036 control chromosomes in the GnomAD database, including 6,661 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 0.29 (6661 hom., cov: 33)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.764
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330751.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	NM_001330751.2		c.69+44279C>A		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.69+44279C>A		intron	N/A	NP_001341754.1
	PPARGC1A	NM_001354827.2		c.69+44279C>A		intron	N/A	NP_001341756.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43545 AN: 151916 Hom.: 6649 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.287 AC: 43586 AN: 152036 Hom.: 6661 Cov.: 33 AF XY: 0.294 AC XY: 21863 AN XY: 74322

African (AFR) AF: 0.182 AC: 7542 AN: 41486

American (AMR) AF: 0.390 AC: 5965 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1131 AN: 3468

East Asian (EAS) AF: 0.377 AC: 1946 AN: 5166

South Asian (SAS) AF: 0.449 AC: 2160 AN: 4816

European-Finnish (FIN) AF: 0.336 AC: 3546 AN: 10550

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20323 AN: 67958

Other (OTH) AF: 0.308 AC: 647 AN: 2104

Alfa AF: 0.283 Hom.: 4173

Bravo AF: 0.284

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.70
PhyloP100		0.76

Splicing

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

Other links and lift over

dbSNP: rs16874778; hg19: chr4-24048812;