NM_001330751.2:c.70-101510G>T

Variant names:

• chr4-23986441-C-A
• rs7682906
• NM_001330751.2:c.70-101510G>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.70-101510G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,850 control chromosomes in the GnomAD database, including 27,032 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 0.59 (27032 hom., cov: 33)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.70-101510G>T		intron_variant	Intron 3 of 14		NP_001317680.1
PPARGC1A	NM_001354825.2	c.70-101510G>T		intron_variant	Intron 2 of 13		NP_001341754.1
PPARGC1A	NM_001354827.2	c.70-101510G>T		intron_variant	Intron 2 of 13		NP_001341756.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89234 AN: 151730 Hom.: 27019 Cov.: 33

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.588 AC: 89277 AN: 151850 Hom.: 27032 Cov.: 33 AF XY: 0.580 AC XY: 43017 AN XY: 74228

African (AFR) AF: 0.685 AC: 28374 AN: 41440

American (AMR) AF: 0.437 AC: 6667 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1962 AN: 3466

East Asian (EAS) AF: 0.316 AC: 1623 AN: 5128

South Asian (SAS) AF: 0.416 AC: 2005 AN: 4822

European-Finnish (FIN) AF: 0.587 AC: 6194 AN: 10560

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.599 AC: 40641 AN: 67886

Other (OTH) AF: 0.548 AC: 1154 AN: 2106

Alfa AF: 0.577 Hom.: 12070

Bravo AF: 0.580

Asia WGS AF: 0.361 AC: 1259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.094
DANN	Benign	0.45
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs7682906; hg19: chr4-23988064;