rs10002590

Variant names:

• chr4-23855612-G-A
• rs10002590
• NM_013261.5:c.235-23861C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-23855612-G-A
• chr4-23855612-G-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.235-23861C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,088 control chromosomes in the GnomAD database, including 1,742 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 0.15 (1742 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.179 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	NM_013261.5	MANE Select	c.235-23861C>T		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.250-23861C>T		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.250-23861C>T		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.235-23861C>T		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000613098.4	TSL:1	c.-147-23861C>T		intron	N/A	ENSP00000481498.1
	PPARGC1A	ENST00000506055.5	TSL:1	n.235-23861C>T		intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22601 AN: 151970 Hom.: 1737 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.149 AC: 22621 AN: 152088 Hom.: 1742 Cov.: 33 AF XY: 0.150 AC XY: 11137 AN XY: 74328

African (AFR) AF: 0.161 AC: 6690 AN: 41476

American (AMR) AF: 0.184 AC: 2817 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3472

East Asian (EAS) AF: 0.174 AC: 901 AN: 5168

South Asian (SAS) AF: 0.170 AC: 816 AN: 4810

European-Finnish (FIN) AF: 0.128 AC: 1357 AN: 10580

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9059 AN: 68000

Other (OTH) AF: 0.148 AC: 313 AN: 2108

Alfa AF: 0.129 Hom.: 549

Bravo AF: 0.156

Asia WGS AF: 0.166 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.37
PhyloP100		-0.031
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: rs10002590; hg19: chr4-23857235;