rs13131226

Variant names:

• chr4-23873358-C-T
• rs13131226
• NM_013261.5:c.234+11394G>A

Variant summary

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

The NM_001330751.2(PPARGC1A):​c.249+11394G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 151,748 control chromosomes in the GnomAD database, including 30,884 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 0.63 (30884 hom., cov: 31)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330751.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	NM_013261.5	MANE Select	c.234+11394G>A		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.249+11394G>A		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.249+11394G>A		intron	N/A	NP_001341754.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	ENST00000264867.7	TSL:1 MANE Select	c.234+11394G>A		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000613098.4	TSL:1	c.-148+7371G>A		intron	N/A	ENSP00000481498.1
	PPARGC1A	ENST00000506055.5	TSL:1	n.234+11394G>A		intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 95975 AN: 151630 Hom.: 30895 Cov.: 31

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.633 AC: 95995 AN: 151748 Hom.: 30884 Cov.: 31 AF XY: 0.631 AC XY: 46784 AN XY: 74144

African (AFR) AF: 0.514 AC: 21270 AN: 41374

American (AMR) AF: 0.583 AC: 8895 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2186 AN: 3466

East Asian (EAS) AF: 0.673 AC: 3461 AN: 5140

South Asian (SAS) AF: 0.674 AC: 3233 AN: 4800

European-Finnish (FIN) AF: 0.692 AC: 7263 AN: 10494

Middle Eastern (MID) AF: 0.710 AC: 206 AN: 290

European-Non Finnish (NFE) AF: 0.700 AC: 47547 AN: 67922

Other (OTH) AF: 0.638 AC: 1343 AN: 2106

Alfa AF: 0.653 Hom.: 11563

Bravo AF: 0.619

Asia WGS AF: 0.663 AC: 2307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.68
PhyloP100		-0.25
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: rs13131226; hg19: chr4-23874981;