rs7680610

Variant names:

• chr4-24116542-A-G
• rs7680610
• NM_001330751.2:c.-99-24907T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-24116542-A-G
• chr4-24116542-A-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.-99-24907T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,078 control chromosomes in the GnomAD database, including 36,909 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 0.69 (36909 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 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.-99-24907T>C		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.-99-24907T>C		intron	N/A	NP_001341754.1
	PPARGC1A	NM_001354827.2		c.-99-24907T>C		intron	N/A	NP_001341756.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105112 AN: 151960 Hom.: 36861 Cov.: 32

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.692 AC: 105223 AN: 152078 Hom.: 36909 Cov.: 32 AF XY: 0.690 AC XY: 51326 AN XY: 74336

African (AFR) AF: 0.808 AC: 33545 AN: 41514

American (AMR) AF: 0.655 AC: 9998 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2117 AN: 3470

East Asian (EAS) AF: 0.575 AC: 2967 AN: 5158

South Asian (SAS) AF: 0.591 AC: 2847 AN: 4816

European-Finnish (FIN) AF: 0.683 AC: 7228 AN: 10582

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44419 AN: 67964

Other (OTH) AF: 0.639 AC: 1346 AN: 2108

Alfa AF: 0.659 Hom.: 131488

Bravo AF: 0.694

Asia WGS AF: 0.606 AC: 2106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.37
DANN	Benign	0.27
PhyloP100		-0.42

Splicing

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

Other links and lift over

dbSNP: rs7680610; hg19: chr4-24118165;