rs7682765

Variant names:

• chr4-23801584-T-C
• rs7682765
• NM_013261.5:c.2293+146A>G

Variant summary

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

The NM_013261.5(PPARGC1A):​c.2293+146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 915,114 control chromosomes in the GnomAD database, including 2,422 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 0.052 (398 hom., cov: 32)
  • Exomes 𝑓: 0.062 (2024 hom.)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207
• Publications: 10 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.2293+146A>G		intron_variant	Intron 12 of 12	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.2293+146A>G		intron_variant	Intron 12 of 12	1	NM_013261.5	ENSP00000264867.2
PPARGC1A	ENST00000613098.4	c.1912+146A>G		intron_variant	Intron 11 of 11	1		ENSP00000481498.1
PPARGC1A	ENST00000506055.5	n.*1508+146A>G		intron_variant	Intron 12 of 12	1		ENSP00000423075.1
PPARGC1A	ENST00000509702.5	n.2333+146A>G		intron_variant	Intron 12 of 14	5

Frequencies

GnomAD3 genomes AF: 0.0518 AC: 7878 AN: 152176 Hom.: 398 Cov.: 32

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0402

GnomAD4 exome AF: 0.0624 AC: 47575 AN: 762820 Hom.: 2024 AF XY: 0.0611 AC XY: 23628 AN XY: 387012

African (AFR) AF: 0.00821 AC: 147 AN: 17910

American (AMR) AF: 0.0186 AC: 368 AN: 19832

Ashkenazi Jewish (ASJ) AF: 0.0232 AC: 365 AN: 15702

East Asian (EAS) AF: 0.00 AC: 0 AN: 32640

South Asian (SAS) AF: 0.0144 AC: 728 AN: 50598

European-Finnish (FIN) AF: 0.160 AC: 6936 AN: 43242

Middle Eastern (MID) AF: 0.00861 AC: 23 AN: 2670

European-Non Finnish (NFE) AF: 0.0682 AC: 37112 AN: 544184

Other (OTH) AF: 0.0526 AC: 1896 AN: 36042

GnomAD4 genome AF: 0.0517 AC: 7877 AN: 152294 Hom.: 398 Cov.: 32 AF XY: 0.0554 AC XY: 4126 AN XY: 74454

African (AFR) AF: 0.0111 AC: 460 AN: 41558

American (AMR) AF: 0.0191 AC: 292 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0145 AC: 70 AN: 4826

European-Finnish (FIN) AF: 0.179 AC: 1895 AN: 10598

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0732 AC: 4980 AN: 68034

Other (OTH) AF: 0.0397 AC: 84 AN: 2114

Alfa AF: 0.0648 Hom.: 228

Bravo AF: 0.0369

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.25
DANN	Benign	0.73
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7682765; hg19: chr4-23803207;