rs16875109

Variant names:

• chr4-24138058-G-A
• rs16875109
• NM_001330751.2:c.-99-46423C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-24138058-G-A
• chr4-24138058-G-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.-99-46423C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,978 control chromosomes in the GnomAD database, including 7,872 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 0.31 (7872 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	NM_001330751.2		c.-99-46423C>T		intron	N/A	NP_001317680.1	Q9UBK2-3
	PPARGC1A	NM_001354825.2		c.-99-46423C>T		intron	N/A	NP_001341754.1	Q9UBK2-3
	PPARGC1A	NM_001354827.2		c.-99-46423C>T		intron	N/A	NP_001341756.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46381 AN: 151860 Hom.: 7865 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.305 AC: 46422 AN: 151978 Hom.: 7872 Cov.: 32 AF XY: 0.308 AC XY: 22883 AN XY: 74302

African (AFR) AF: 0.447 AC: 18524 AN: 41404

American (AMR) AF: 0.334 AC: 5103 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3466

East Asian (EAS) AF: 0.264 AC: 1360 AN: 5144

South Asian (SAS) AF: 0.362 AC: 1747 AN: 4820

European-Finnish (FIN) AF: 0.238 AC: 2518 AN: 10580

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15440 AN: 67964

Other (OTH) AF: 0.281 AC: 592 AN: 2106

Alfa AF: 0.263 Hom.: 719

Bravo AF: 0.318

Asia WGS AF: 0.310 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.57
PhyloP100		0.039

Splicing

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

Other links and lift over

dbSNP: rs16875109; hg19: chr4-24139681;