4-23786718-T-C

Variant names:

• chr4-23786718-T-C
• rs2970882
• ENST00000509702.5:n.2433+9108A>G

Variant summary

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

The ENST00000509702.5(PPARGC1A):​n.2433+9108A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,658 control chromosomes in the GnomAD database, including 11,476 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 0.38 (11476 hom., cov: 30)
• Consequence: PPARGC1A ENST00000509702.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.856
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000509702.5	n.2433+9108A>G		intron_variant	Intron 13 of 14	5

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58251 AN: 151540 Hom.: 11456 Cov.: 30

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.385 AC: 58328 AN: 151658 Hom.: 11476 Cov.: 30 AF XY: 0.388 AC XY: 28725 AN XY: 74108

African (AFR) AF: 0.466 AC: 19262 AN: 41346

American (AMR) AF: 0.376 AC: 5730 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 930 AN: 3456

East Asian (EAS) AF: 0.350 AC: 1789 AN: 5116

South Asian (SAS) AF: 0.407 AC: 1954 AN: 4796

European-Finnish (FIN) AF: 0.418 AC: 4392 AN: 10504

Middle Eastern (MID) AF: 0.341 AC: 99 AN: 290

European-Non Finnish (NFE) AF: 0.339 AC: 23021 AN: 67896

Other (OTH) AF: 0.374 AC: 788 AN: 2108

Alfa AF: 0.347 Hom.: 31101

Bravo AF: 0.378

Asia WGS AF: 0.398 AC: 1383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.46
DANN	Benign	0.58
PhyloP100		-0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2970882; hg19: chr4-23788341;