4-23907267-C-A

Variant names:

• chr4-23907267-C-A
• rs13108219
• NM_001330751.2:c.70-22336G>T

Variant summary

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

The NM_001330751.2(PPARGC1A):​c.70-22336G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,062 control chromosomes in the GnomAD database, including 2,589 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 0.17 (2589 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330751.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	NM_001330751.2		c.70-22336G>T		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.70-22336G>T		intron	N/A	NP_001341754.1
	PPARGC1A	NM_001354827.2		c.70-22336G>T		intron	N/A	NP_001341756.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25694 AN: 151944 Hom.: 2591 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.169 AC: 25721 AN: 152062 Hom.: 2589 Cov.: 32 AF XY: 0.171 AC XY: 12727 AN XY: 74348

African (AFR) AF: 0.244 AC: 10128 AN: 41456

American (AMR) AF: 0.130 AC: 1980 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3470

East Asian (EAS) AF: 0.363 AC: 1875 AN: 5160

South Asian (SAS) AF: 0.268 AC: 1293 AN: 4824

European-Finnish (FIN) AF: 0.112 AC: 1183 AN: 10560

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.119 AC: 8114 AN: 67988

Other (OTH) AF: 0.175 AC: 371 AN: 2116

Alfa AF: 0.137 Hom.: 4680

Bravo AF: 0.174

Asia WGS AF: 0.296 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.76
PhyloP100		-0.089

Splicing

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

Other links and lift over

dbSNP: rs13108219; hg19: chr4-23908890;