rs16874271

chr4-23878104-A-G

Variant summary

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

The NM_013261.5(PPARGC1A):c.234+6648T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 152,228 control chromosomes in the GnomAD database, including 414 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 0.071 (414 hom., cov: 31)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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 -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 = 0.0833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1A	NM_013261.5	c.234+6648T>C		intron_variant		ENST00000264867.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.234+6648T>C		intron_variant		1	NM_013261.5	P1

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10719 AN: 152110 Hom.: 413 Cov.: 31

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0589

Gnomad FIN AF: 0.0370

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0754

Gnomad OTH AF: 0.0736

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0705 AC: 10734 AN: 152228 Hom.: 414 Cov.: 31 AF XY: 0.0682 AC XY: 5074 AN XY: 74418

Gnomad4 AFR AF: 0.0856

Gnomad4 AMR AF: 0.0559

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0592

Gnomad4 FIN AF: 0.0370

Gnomad4 NFE AF: 0.0754

Gnomad4 OTH AF: 0.0728

Alfa AF: 0.0747 Hom.: 53

Bravo AF: 0.0711

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.023
Dann	Benign	0.42

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: rs16874271; hg19: chr4-23879727;