chr4-23859191-A-C

Variant names:

• chr4-23859191-A-C
• rs12640088
• NM_013261.5:c.234+25561T>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+25561T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,164 control chromosomes in the GnomAD database, including 1,276 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 0.12 (1276 hom., cov: 32)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.112
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.234+25561T>G		intron_variant	Intron 2 of 12	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.234+25561T>G		intron_variant	Intron 2 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18621 AN: 152048 Hom.: 1275 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.0879

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.0584

Gnomad FIN AF: 0.0904

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.122 AC: 18631 AN: 152164 Hom.: 1276 Cov.: 32 AF XY: 0.119 AC XY: 8822 AN XY: 74388

African (AFR) AF: 0.113 AC: 4687 AN: 41526

American (AMR) AF: 0.0877 AC: 1341 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3470

East Asian (EAS) AF: 0.124 AC: 642 AN: 5174

South Asian (SAS) AF: 0.0592 AC: 286 AN: 4828

European-Finnish (FIN) AF: 0.0904 AC: 956 AN: 10576

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9369 AN: 67990

Other (OTH) AF: 0.124 AC: 261 AN: 2112

Alfa AF: 0.129 Hom.: 446

Bravo AF: 0.124

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.46
PhyloP100		-0.11
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: rs12640088; hg19: chr4-23860814;