chr4-23888158-A-G

Position:

• chr4-23888158-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013261.5(PPARGC1A):​c.54+1746T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,232 control chromosomes in the GnomAD database, including 56,355 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 0.86 (56355 hom., cov: 34)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

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]

PPARGC1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.54+1746T>C		intron_variant		ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.54+1746T>C		intron_variant		1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130218 AN: 152114 Hom.: 56309 Cov.: 34

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.834

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.856 AC: 130310 AN: 152232 Hom.: 56355 Cov.: 34 AF XY: 0.848 AC XY: 63066 AN XY: 74400

Gnomad4 AFR AF: 0.965

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.847

Alfa AF: 0.843 Hom.: 20540

Bravo AF: 0.859

Asia WGS AF: 0.737 AC: 2563 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	0.048
DANN	Benign	0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2970873; hg19: chr4-23889781;