rs10030083

Variant names:

• chr4-23899799-C-A
• rs10030083
• NM_001330751.2:c.70-14868G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-23899799-C-A
• chr4-23899799-C-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.70-14868G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 151,954 control chromosomes in the GnomAD database, including 2,914 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 (2914 hom., cov: 32)
• Consequence: PPARGC1A NM_001330751.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_001330751.2	c.70-14868G>T		intron_variant	Intron 3 of 14		NP_001317680.1
PPARGC1A	NM_001354825.2	c.70-14868G>T		intron_variant	Intron 2 of 13		NP_001341754.1
PPARGC1A	NM_001354827.2	c.70-14868G>T		intron_variant	Intron 2 of 13		NP_001341756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000514494.1	n.96+4195G>T		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26480 AN: 151836 Hom.: 2910 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.174 AC: 26505 AN: 151954 Hom.: 2914 Cov.: 32 AF XY: 0.178 AC XY: 13251 AN XY: 74272

African (AFR) AF: 0.291 AC: 12054 AN: 41392

American (AMR) AF: 0.119 AC: 1819 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3466

East Asian (EAS) AF: 0.367 AC: 1891 AN: 5146

South Asian (SAS) AF: 0.222 AC: 1069 AN: 4812

European-Finnish (FIN) AF: 0.144 AC: 1526 AN: 10574

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7106 AN: 67992

Other (OTH) AF: 0.166 AC: 350 AN: 2110

Alfa AF: 0.127 Hom.: 6215

Bravo AF: 0.178

Asia WGS AF: 0.269 AC: 934 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.24
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs10030083; hg19: chr4-23901422;