rs10489100

Variant names:

• chr4-24079823-C-G
• rs10489100
• NM_001330751.2:c.69+11645G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-24079823-C-G
• chr4-24079823-C-T

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+11645G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 152,050 control chromosomes in the GnomAD database, including 610 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 0.085 (610 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• 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]

ENSG00000304770 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.69+11645G>C		intron_variant	Intron 3 of 14		NP_001317680.1
PPARGC1A	NM_001354825.2	c.69+11645G>C		intron_variant	Intron 2 of 13		NP_001341754.1
PPARGC1A	NM_001354827.2	c.69+11645G>C		intron_variant	Intron 2 of 13		NP_001341756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000304770	ENST00000806163.1	n.172+11645G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 12830 AN: 151932 Hom.: 609 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.0874

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0263

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0722

Gnomad OTH AF: 0.0808

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

GnomAD4 genome AF: 0.0845 AC: 12853 AN: 152050 Hom.: 610 Cov.: 32 AF XY: 0.0830 AC XY: 6169 AN XY: 74324

African (AFR) AF: 0.116 AC: 4835 AN: 41516

American (AMR) AF: 0.0459 AC: 700 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0874 AC: 303 AN: 3468

East Asian (EAS) AF: 0.172 AC: 890 AN: 5168

South Asian (SAS) AF: 0.119 AC: 572 AN: 4816

European-Finnish (FIN) AF: 0.0263 AC: 279 AN: 10604

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0722 AC: 4900 AN: 67892

Other (OTH) AF: 0.0828 AC: 175 AN: 2114

Alfa AF: 0.0307 Hom.: 24

Bravo AF: 0.0867

Asia WGS AF: 0.135 AC: 467 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs10489100; hg19: chr4-24081446;