4-23825992-G-A

Variant names:

• chr4-23825992-G-A
• rs2970856
• NM_013261.5:c.758-1484C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013261.5(PPARGC1A):​c.758-1484C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,130 control chromosomes in the GnomAD database, including 51,315 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 0.82 (51315 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.758-1484C>T		intron_variant	Intron 5 of 12	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.758-1484C>T		intron_variant	Intron 5 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124646 AN: 152012 Hom.: 51259 Cov.: 33

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.820 AC: 124760 AN: 152130 Hom.: 51315 Cov.: 33 AF XY: 0.824 AC XY: 61243 AN XY: 74364

African (AFR) AF: 0.875 AC: 36315 AN: 41514

American (AMR) AF: 0.858 AC: 13109 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2947 AN: 3472

East Asian (EAS) AF: 0.775 AC: 4001 AN: 5162

South Asian (SAS) AF: 0.831 AC: 4004 AN: 4820

European-Finnish (FIN) AF: 0.821 AC: 8694 AN: 10584

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.779 AC: 52958 AN: 67992

Other (OTH) AF: 0.835 AC: 1762 AN: 2110

Alfa AF: 0.806 Hom.: 19169

Bravo AF: 0.824

Asia WGS AF: 0.846 AC: 2941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.61
DANN	Benign	0.38
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2970856; hg19: chr4-23827615;