NM_013261.5:c.2020-2810G>T

Variant names:

• chr4-23805155-C-A
• rs1873532
• NM_013261.5:c.2020-2810G>T

Variant summary

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

The NM_013261.5(PPARGC1A):​c.2020-2810G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,684 control chromosomes in the GnomAD database, including 9,576 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 0.34 (9576 hom., cov: 31)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 5 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 (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013261.5. 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_013261.5	MANE Select	c.2020-2810G>T		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.2035-2810G>T		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.2035-2810G>T		intron	N/A	NP_001341754.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	ENST00000264867.7	TSL:1 MANE Select	c.2020-2810G>T		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000613098.4	TSL:1	c.1639-2810G>T		intron	N/A	ENSP00000481498.1
	PPARGC1A	ENST00000506055.5	TSL:1	n.*1235-2810G>T		intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52318 AN: 151566 Hom.: 9583 Cov.: 31

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.345 AC: 52316 AN: 151684 Hom.: 9576 Cov.: 31 AF XY: 0.343 AC XY: 25395 AN XY: 74116

African (AFR) AF: 0.234 AC: 9682 AN: 41344

American (AMR) AF: 0.352 AC: 5359 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1679 AN: 3472

East Asian (EAS) AF: 0.426 AC: 2179 AN: 5118

South Asian (SAS) AF: 0.330 AC: 1591 AN: 4814

European-Finnish (FIN) AF: 0.349 AC: 3660 AN: 10502

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.397 AC: 26947 AN: 67890

Other (OTH) AF: 0.383 AC: 803 AN: 2098

Alfa AF: 0.382 Hom.: 28242

Bravo AF: 0.344

Asia WGS AF: 0.377 AC: 1309 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.47
PhyloP100		0.055
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: rs1873532; hg19: chr4-23806778;