4-24240600-T-C

Variant names:

• chr4-24240600-T-C
• rs7666134
• NM_001330751.2:c.-100+17603A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001330751.2(PPARGC1A):​c.-100+17603A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0812 in 152,280 control chromosomes in the GnomAD database, including 598 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 0.081 (598 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.-100+17603A>G		intron_variant	Intron 2 of 14		NP_001317680.1
PPARGC1A	NM_001354825.2	c.-99-148965A>G		intron_variant	Intron 1 of 13		NP_001341754.1
PPARGC1A	NM_001354827.2	c.-99-148965A>G		intron_variant	Intron 1 of 13		NP_001341756.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12349 AN: 152162 Hom.: 598 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.0500

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0622

Gnomad FIN AF: 0.0352

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0777

Gnomad OTH AF: 0.0779

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

GnomAD4 genome AF: 0.0812 AC: 12364 AN: 152280 Hom.: 598 Cov.: 32 AF XY: 0.0788 AC XY: 5865 AN XY: 74468

African (AFR) AF: 0.122 AC: 5055 AN: 41550

American (AMR) AF: 0.0499 AC: 763 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 252 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0623 AC: 301 AN: 4834

European-Finnish (FIN) AF: 0.0352 AC: 374 AN: 10618

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0777 AC: 5288 AN: 68020

Other (OTH) AF: 0.0771 AC: 163 AN: 2114

Alfa AF: 0.0781 Hom.: 772

Bravo AF: 0.0830

Asia WGS AF: 0.0280 AC: 96 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Benign	0.68
PhyloP100		1.7

Splicing

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

Other links and lift over

dbSNP: rs7666134; hg19: chr4-24242223;