4-23893662-C-T

Variant names:

• chr4-23893662-C-T
• rs2970866
• NM_001330751.2:c.70-8731G>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.70-8731G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,058 control chromosomes in the GnomAD database, including 48,201 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 0.79 (48201 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.70-8731G>A		intron_variant	Intron 3 of 14		NP_001317680.1
PPARGC1A	NM_001354825.2	c.70-8731G>A		intron_variant	Intron 2 of 13		NP_001341754.1
PPARGC1A	NM_001354827.2	c.70-8731G>A		intron_variant	Intron 2 of 13		NP_001341756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000507342.5	n.53-3449G>A		intron_variant	Intron 1 of 3	3
PPARGC1A	ENST00000514494.1	n.97-8731G>A		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119783 AN: 151940 Hom.: 48161 Cov.: 32

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.788 AC: 119863 AN: 152058 Hom.: 48201 Cov.: 32 AF XY: 0.780 AC XY: 57974 AN XY: 74304

African (AFR) AF: 0.928 AC: 38508 AN: 41514

American (AMR) AF: 0.584 AC: 8903 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2642 AN: 3470

East Asian (EAS) AF: 0.617 AC: 3191 AN: 5168

South Asian (SAS) AF: 0.731 AC: 3524 AN: 4824

European-Finnish (FIN) AF: 0.735 AC: 7751 AN: 10550

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52813 AN: 67972

Other (OTH) AF: 0.778 AC: 1644 AN: 2112

Alfa AF: 0.785 Hom.: 6137

Bravo AF: 0.778

Asia WGS AF: 0.680 AC: 2364 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.50
DANN	Benign	0.52
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs2970866; hg19: chr4-23895285;