chr4-23880896-A-G

Position:

• chr4-23880896-A-G

Variant summary

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

The NM_001330753.2(PPARGC1A):​c.-315T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,138 control chromosomes in the GnomAD database, including 4,371 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 0.21 (4370 hom., cov: 32)
  • Exomes 𝑓: 0.17 (1 hom.)
• Consequence: PPARGC1A NM_001330753.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226

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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.234+3856T>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.234+3856T>C		intron_variant		1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32595 AN: 152008 Hom.: 4372 Cov.: 32

Gnomad AFR AF: 0.0950

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.0314

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.167 AC: 2 AN: 12 Hom.: 1 Cov.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.214 AC: 32592 AN: 152126 Hom.: 4370 Cov.: 32 AF XY: 0.214 AC XY: 15930 AN XY: 74344

Gnomad4 AFR AF: 0.0948

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.0315

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.201

Alfa AF: 0.237 Hom.: 931

Bravo AF: 0.188

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.4
DANN	Benign	0.60

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: rs11734408; hg19: chr4-23882519;