rs7674429

Positions:

• chr4-23879725-C-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+5027G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,076 control chromosomes in the GnomAD database, including 6,221 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 0.25 (6221 hom., cov: 32)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_013261.5	c.234+5027G>A		intron_variant		ENST00000264867.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.234+5027G>A		intron_variant		1	NM_013261.5	P1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38553 AN: 151958 Hom.: 6214 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.254 AC: 38603 AN: 152076 Hom.: 6221 Cov.: 32 AF XY: 0.256 AC XY: 19020 AN XY: 74326

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.241

Alfa AF: 0.189 Hom.: 582

Bravo AF: 0.272

Asia WGS AF: 0.366 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.099
DANN	Benign	0.62

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: rs7674429; hg19: chr4-23881348;