rs6448228

chr4-23860519-A-Gchr4-23860519-A-T

Variant summary

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

The NM_013261.5(PPARGC1A):c.234+24233T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,962 control chromosomes in the GnomAD database, including 12,160 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 0.40 (12160 hom., cov: 31)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_013261.5	c.234+24233T>C		intron_variant		ENST00000264867.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.234+24233T>C		intron_variant		1	NM_013261.5	P1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60653 AN: 151844 Hom.: 12137 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.400 AC: 60719 AN: 151962 Hom.: 12160 Cov.: 31 AF XY: 0.401 AC XY: 29792 AN XY: 74270

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.412

Alfa AF: 0.399 Hom.: 1696

Bravo AF: 0.398

Asia WGS AF: 0.465 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.7
Dann	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs6448228; hg19: chr4-23862142;