rs3774902

Positions:

• chr4-23889159-G-A

Variant summary

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

The NM_013261.5(PPARGC1A):​c.54+745C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0572 in 985,174 control chromosomes in the GnomAD database, including 2,512 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 0.090 (998 hom., cov: 32)
  • Exomes 𝑓: 0.051 (1514 hom.)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462

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=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.54+745C>T		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+745C>T		intron_variant		1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 13689 AN: 152010 Hom.: 995 Cov.: 32

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.00881

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0902

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0512

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0512 AC: 42623 AN: 833046 Hom.: 1514 Cov.: 31 AF XY: 0.0510 AC XY: 19621 AN XY: 384688

Gnomad4 AFR exome AF: 0.0791

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.0992

Gnomad4 EAS exome AF: 0.355

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.0797

Gnomad4 NFE exome AF: 0.0450

Gnomad4 OTH exome AF: 0.0830

GnomAD4 genome AF: 0.0900 AC: 13695 AN: 152128 Hom.: 998 Cov.: 32 AF XY: 0.0968 AC XY: 7201 AN XY: 74368

Gnomad4 AFR AF: 0.0778

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.0902

Gnomad4 NFE AF: 0.0512

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0687 Hom.: 524

Bravo AF: 0.0977

Asia WGS AF: 0.267 AC: 924 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.88

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: rs3774902; hg19: chr4-23890782;