4-23815214-C-T

Variant names:

• chr4-23815214-C-T
• rs3755862
• NM_013261.5:c.878-609G>A

Variant summary

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

The NM_013261.5(PPARGC1A):​c.878-609G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0733 in 151,778 control chromosomes in the GnomAD database, including 472 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 0.073 (472 hom., cov: 31)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.878-609G>A		intron_variant	Intron 7 of 12	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.878-609G>A		intron_variant	Intron 7 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.0733 AC: 11124 AN: 151676 Hom.: 472 Cov.: 31

Gnomad AFR AF: 0.0649

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0559

Gnomad OTH AF: 0.0801

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

GnomAD4 genome AF: 0.0733 AC: 11127 AN: 151778 Hom.: 472 Cov.: 31 AF XY: 0.0787 AC XY: 5837 AN XY: 74152

African (AFR) AF: 0.0648 AC: 2681 AN: 41382

American (AMR) AF: 0.0864 AC: 1315 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 281 AN: 3472

East Asian (EAS) AF: 0.185 AC: 949 AN: 5138

South Asian (SAS) AF: 0.148 AC: 713 AN: 4806

European-Finnish (FIN) AF: 0.104 AC: 1094 AN: 10506

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.0559 AC: 3796 AN: 67942

Other (OTH) AF: 0.0790 AC: 166 AN: 2102

Alfa AF: 0.0545 Hom.: 176

Bravo AF: 0.0698

Asia WGS AF: 0.142 AC: 490 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.80
PhyloP100		-1.1
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: rs3755862; hg19: chr4-23816837;