4-23888959-T-C

Position:

• chr4-23888959-T-C

Variant summary

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

The NM_013261.5(PPARGC1A):​c.54+945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 984,754 control chromosomes in the GnomAD database, including 159,756 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 0.59 (26913 hom., cov: 31)
  • Exomes 𝑓: 0.56 (132843 hom.)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.54+945A>G		intron_variant		ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.54+945A>G		intron_variant		1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89431 AN: 151790 Hom.: 26880 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.610

GnomAD4 exome AF: 0.564 AC: 469709 AN: 832846 Hom.: 132843 Cov.: 32 AF XY: 0.564 AC XY: 217020 AN XY: 384620

Gnomad4 AFR exome AF: 0.721

Gnomad4 AMR exome AF: 0.529

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.603

Gnomad4 SAS exome AF: 0.559

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.559

Gnomad4 OTH exome AF: 0.585

GnomAD4 genome AF: 0.589 AC: 89506 AN: 151908 Hom.: 26913 Cov.: 31 AF XY: 0.583 AC XY: 43278 AN XY: 74242

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.606

Alfa AF: 0.565 Hom.: 5914

Bravo AF: 0.610

Asia WGS AF: 0.577 AC: 2008 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2970871; hg19: chr4-23890582;