4-23795377-C-T

Position:

• chr4-23795377-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000264867.7(PPARGC1A):​c.*445G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 147,626 control chromosomes in the GnomAD database, including 21,378 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 0.53 (21329 hom., cov: 24)
  • Exomes 𝑓: 0.45 (49 hom.)
• Consequence: PPARGC1A ENST00000264867.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.*445G>A		3_prime_UTR_variant	13/13	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.*445G>A		3_prime_UTR_variant	13/13	1	NM_013261.5	ENSP00000264867	P1
PPARGC1A	ENST00000613098.4	c.*445G>A		3_prime_UTR_variant	12/12	1		ENSP00000481498
PPARGC1A	ENST00000509702.5	n.2433+449G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.533 AC: 78444 AN: 147122 Hom.: 21328 Cov.: 24

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.645

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.567

GnomAD4 exome AF: 0.452 AC: 196 AN: 434 Hom.: 49 Cov.: 0 AF XY: 0.461 AC XY: 119 AN XY: 258

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.833

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.480

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.533 AC: 78468 AN: 147192 Hom.: 21329 Cov.: 24 AF XY: 0.534 AC XY: 38165 AN XY: 71480

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.566

Alfa AF: 0.512 Hom.: 33339

Bravo AF: 0.537

Asia WGS AF: 0.651 AC: 2268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.91

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: rs6821591; hg19: chr4-23797000;