4-24172160-A-T

Variant names:

• chr4-24172160-A-T
• rs4697438
• NM_001330751.2:c.-99-80525T>A

Variant summary

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

The NM_001330751.2(PPARGC1A):​c.-99-80525T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 152,148 control chromosomes in the GnomAD database, including 53,658 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 0.83 (53658 hom., cov: 31)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.-99-80525T>A		intron_variant	Intron 2 of 14		NP_001317680.1
PPARGC1A	NM_001354825.2	c.-99-80525T>A		intron_variant	Intron 1 of 13		NP_001341754.1
PPARGC1A	NM_001354827.2	c.-99-80525T>A		intron_variant	Intron 1 of 13		NP_001341756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126147 AN: 152030 Hom.: 53621 Cov.: 31

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.944

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.830 AC: 126242 AN: 152148 Hom.: 53658 Cov.: 31 AF XY: 0.835 AC XY: 62123 AN XY: 74394

African (AFR) AF: 0.621 AC: 25755 AN: 41462

American (AMR) AF: 0.884 AC: 13513 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.944 AC: 3276 AN: 3472

East Asian (EAS) AF: 0.867 AC: 4474 AN: 5160

South Asian (SAS) AF: 0.909 AC: 4372 AN: 4808

European-Finnish (FIN) AF: 0.966 AC: 10260 AN: 10622

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.909 AC: 61806 AN: 68022

Other (OTH) AF: 0.848 AC: 1790 AN: 2112

Alfa AF: 0.874 Hom.: 6893

Bravo AF: 0.815

Asia WGS AF: 0.889 AC: 3089 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.80
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs4697438; hg19: chr4-24173783;