rs2279525

Variant names:

• chr4-23792629-T-C
• rs2279525
• NM_013261.5:c.*3193A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-23792629-T-C
• chr4-23792629-T-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.*3193A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,194 control chromosomes in the GnomAD database, including 8,409 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 0.33 (8382 hom., cov: 31)
  • Exomes 𝑓: 0.34 (27 hom.)
• Consequence: PPARGC1A NM_013261.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 12 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=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.*3193A>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.*3193A>G		3_prime_UTR_variant	Exon 13 of 13	1	NM_013261.5	ENSP00000264867.2
PPARGC1A	ENST00000509702.5	n.2433+3197A>G		intron_variant	Intron 13 of 14	5

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49439 AN: 151644 Hom.: 8363 Cov.: 31

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.336 AC: 145 AN: 432 Hom.: 27 Cov.: 0 AF XY: 0.331 AC XY: 86 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.336 AC: 143 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.326 AC: 49508 AN: 151762 Hom.: 8382 Cov.: 31 AF XY: 0.326 AC XY: 24167 AN XY: 74146

African (AFR) AF: 0.413 AC: 17099 AN: 41384

American (AMR) AF: 0.307 AC: 4666 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 844 AN: 3460

East Asian (EAS) AF: 0.189 AC: 975 AN: 5162

South Asian (SAS) AF: 0.282 AC: 1349 AN: 4792

European-Finnish (FIN) AF: 0.330 AC: 3479 AN: 10536

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20106 AN: 67920

Other (OTH) AF: 0.310 AC: 652 AN: 2104

Alfa AF: 0.297 Hom.: 24215

Bravo AF: 0.322

Asia WGS AF: 0.276 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		1.5
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: rs2279525; hg19: chr4-23794252;