rs640050

Positions:

• chr4-24046063-A-G
• chr4-24046063-A-T

Variant summary

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

The NM_001330751.2(PPARGC1A):​c.69+45405T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,014 control chromosomes in the GnomAD database, including 21,313 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 0.52 (21313 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.680

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.69+45405T>C		intron_variant			NP_001317680.1
PPARGC1A	NM_001354825.2	c.69+45405T>C		intron_variant			NP_001341754.1
PPARGC1A	NM_001354827.2	c.69+45405T>C		intron_variant			NP_001341756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79296 AN: 151896 Hom.: 21318 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.522 AC: 79318 AN: 152014 Hom.: 21313 Cov.: 32 AF XY: 0.520 AC XY: 38602 AN XY: 74274

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.524

Alfa AF: 0.570 Hom.: 15430

Bravo AF: 0.509

Asia WGS AF: 0.414 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.0
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs640050; hg19: chr4-24047686;