chr4-23864716-T-C

Variant names:

• chr4-23864716-T-C
• rs10213440
• NM_013261.5:c.234+20036A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_013261.5(PPARGC1A):​c.234+20036A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,148 control chromosomes in the GnomAD database, including 3,145 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 0.20 (3145 hom., cov: 32)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.660
• Publications: 10 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 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+20036A>G		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.249+20036A>G		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.249+20036A>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+20036A>G		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000613098.4	TSL:1	c.-148+16013A>G		intron	N/A	ENSP00000481498.1
	PPARGC1A	ENST00000506055.5	TSL:1	n.234+20036A>G		intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29906 AN: 152030 Hom.: 3144 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.197 AC: 29936 AN: 152148 Hom.: 3145 Cov.: 32 AF XY: 0.195 AC XY: 14504 AN XY: 74394

African (AFR) AF: 0.248 AC: 10311 AN: 41496

American (AMR) AF: 0.130 AC: 1986 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 831 AN: 3472

East Asian (EAS) AF: 0.212 AC: 1094 AN: 5164

South Asian (SAS) AF: 0.158 AC: 765 AN: 4830

European-Finnish (FIN) AF: 0.156 AC: 1648 AN: 10582

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12421 AN: 68000

Other (OTH) AF: 0.191 AC: 405 AN: 2116

Alfa AF: 0.185 Hom.: 10145

Bravo AF: 0.199

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		0.66
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: rs10213440; hg19: chr4-23866339;