rs3774923

Positions:

• chr4-23793441-C-T

Variant summary

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

The NM_013261.5(PPARGC1A):​c.*2381G>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 0.0545 in 152,486 control chromosomes in the GnomAD database, including 314 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 0.055 (312 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2 hom.)
• Consequence: PPARGC1A NM_013261.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58

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=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_013261.5	c.*2381G>A		3_prime_UTR_variant	13/13	ENST00000264867.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.*2381G>A		3_prime_UTR_variant	13/13	1	NM_013261.5	P1
PPARGC1A	ENST00000509702.5	n.2433+2385G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0546 AC: 8295 AN: 152008 Hom.: 311 Cov.: 32

Gnomad AFR AF: 0.0454

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0598

GnomAD4 exome AF: 0.0559 AC: 20 AN: 358 Hom.: 2 Cov.: 0 AF XY: 0.0514 AC XY: 11 AN XY: 214

Gnomad4 FIN exome AF: 0.0571

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0545 AC: 8293 AN: 152128 Hom.: 312 Cov.: 32 AF XY: 0.0589 AC XY: 4379 AN XY: 74370

Gnomad4 AFR AF: 0.0452

Gnomad4 AMR AF: 0.0643

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0802

Gnomad4 NFE AF: 0.0380

Gnomad4 OTH AF: 0.0587

Alfa AF: 0.0449 Hom.: 253

Bravo AF: 0.0523

Asia WGS AF: 0.134 AC: 464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.84

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: rs3774923; hg19: chr4-23795064;