NM_013261.5:c.234+18752C>G

Variant names:

• chr4-23866000-G-C
• rs13113110
• NM_013261.5:c.234+18752C>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.234+18752C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,058 control chromosomes in the GnomAD database, including 2,975 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 0.18 (2975 hom., cov: 33)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.245 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.234+18752C>G		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.249+18752C>G		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.249+18752C>G		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.234+18752C>G		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000613098.4	TSL:1	c.-148+14729C>G		intron	N/A	ENSP00000481498.1
	PPARGC1A	ENST00000506055.5	TSL:1	n.234+18752C>G		intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27314 AN: 151934 Hom.: 2970 Cov.: 33

Gnomad AFR AF: 0.0498

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

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: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.180 AC: 27323 AN: 152052 Hom.: 2975 Cov.: 33 AF XY: 0.184 AC XY: 13663 AN XY: 74316

African (AFR) AF: 0.0498 AC: 2065 AN: 41498

American (AMR) AF: 0.251 AC: 3836 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1094 AN: 5158

South Asian (SAS) AF: 0.219 AC: 1053 AN: 4810

European-Finnish (FIN) AF: 0.260 AC: 2748 AN: 10562

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.221 AC: 15032 AN: 67970

Other (OTH) AF: 0.199 AC: 421 AN: 2112

Alfa AF: 0.105 Hom.: 171

Bravo AF: 0.172

Asia WGS AF: 0.226 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.40
DANN	Benign	0.49
PhyloP100		-0.56
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: rs13113110; hg19: chr4-23867623;