rs2324240

Variant names:

• chr4-23960504-T-A
• rs2324240
• NM_001330751.2:c.70-75573A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-23960504-T-A
• chr4-23960504-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330751.2(PPARGC1A):​c.70-75573A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,154 control chromosomes in the GnomAD database, including 2,462 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 0.15 (2462 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 1 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 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.70-75573A>T		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.70-75573A>T		intron	N/A	NP_001341754.1
	PPARGC1A	NM_001354827.2		c.70-75573A>T		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: 0.153 AC: 23204 AN: 152036 Hom.: 2456 Cov.: 32

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.153 AC: 23211 AN: 152154 Hom.: 2462 Cov.: 32 AF XY: 0.159 AC XY: 11850 AN XY: 74398

African (AFR) AF: 0.0390 AC: 1622 AN: 41540

American (AMR) AF: 0.295 AC: 4504 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3472

East Asian (EAS) AF: 0.304 AC: 1573 AN: 5170

South Asian (SAS) AF: 0.223 AC: 1072 AN: 4814

European-Finnish (FIN) AF: 0.221 AC: 2345 AN: 10594

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10971 AN: 67976

Other (OTH) AF: 0.144 AC: 304 AN: 2112

Alfa AF: 0.154 Hom.: 255

Bravo AF: 0.153

Asia WGS AF: 0.240 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.6
DANN	Benign	0.81
PhyloP100		0.037

Splicing

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

Other links and lift over

dbSNP: rs2324240; hg19: chr4-23962127;