NM_013261.5:c.2293+2166G>A

Variant names:

• chr4-23799564-C-T
• rs12650562
• NM_013261.5:c.2293+2166G>A

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+2166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,010 control chromosomes in the GnomAD database, including 16,777 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 0.46 (16777 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 14 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.2293+2166G>A		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+2166G>A		intron_variant	Intron 12 of 12	1	NM_013261.5	ENSP00000264867.2
PPARGC1A	ENST00000613098.4	c.1912+2166G>A		intron_variant	Intron 11 of 11	1		ENSP00000481498.1
PPARGC1A	ENST00000506055.5	n.*1508+2166G>A		intron_variant	Intron 12 of 12	1		ENSP00000423075.1
PPARGC1A	ENST00000509702.5	n.2333+2166G>A		intron_variant	Intron 12 of 14	5

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70592 AN: 151892 Hom.: 16769 Cov.: 33

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.465 AC: 70641 AN: 152010 Hom.: 16777 Cov.: 33 AF XY: 0.461 AC XY: 34213 AN XY: 74282

African (AFR) AF: 0.505 AC: 20948 AN: 41454

American (AMR) AF: 0.424 AC: 6485 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1999 AN: 3470

East Asian (EAS) AF: 0.498 AC: 2563 AN: 5146

South Asian (SAS) AF: 0.479 AC: 2309 AN: 4818

European-Finnish (FIN) AF: 0.384 AC: 4050 AN: 10554

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30756 AN: 67972

Other (OTH) AF: 0.498 AC: 1051 AN: 2110

Alfa AF: 0.468 Hom.: 51566

Bravo AF: 0.473

Asia WGS AF: 0.508 AC: 1771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.37
DANN	Benign	0.73
PhyloP100		-2.0
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: rs12650562; hg19: chr4-23801187;