NM_001330751.2:c.69+81483G>A

Variant names:

• chr4-24009985-C-T
• rs7672552
• NM_001330751.2:c.69+81483G>A

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+81483G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,962 control chromosomes in the GnomAD database, including 25,703 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 0.57 (25703 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 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.69+81483G>A		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.69+81483G>A		intron	N/A	NP_001341754.1
	PPARGC1A	NM_001354827.2		c.69+81483G>A		intron	N/A	NP_001341756.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87228 AN: 151844 Hom.: 25697 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.574 AC: 87265 AN: 151962 Hom.: 25703 Cov.: 32 AF XY: 0.567 AC XY: 42127 AN XY: 74264

African (AFR) AF: 0.669 AC: 27721 AN: 41458

American (AMR) AF: 0.440 AC: 6709 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1833 AN: 3464

East Asian (EAS) AF: 0.342 AC: 1763 AN: 5150

South Asian (SAS) AF: 0.415 AC: 2000 AN: 4818

European-Finnish (FIN) AF: 0.580 AC: 6131 AN: 10568

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39322 AN: 67956

Other (OTH) AF: 0.535 AC: 1126 AN: 2104

Alfa AF: 0.568 Hom.: 78674

Bravo AF: 0.567

Asia WGS AF: 0.368 AC: 1283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.44
PhyloP100		-0.033

Splicing

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

Other links and lift over

dbSNP: rs7672552; hg19: chr4-24011608;