rs2130925

Variant names:

• chr4-23779969-C-T
• rs2130925
• ENST00000506514.1:n.92+288C>T

Variant summary

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

The ENST00000506514.1(ENSG00000249453):​n.92+288C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,058 control chromosomes in the GnomAD database, including 1,715 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 0.12 (1715 hom., cov: 32)
• Consequence: ENSG00000249453 ENST00000506514.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227
• Publications: 0 publications found

Genes affected

ENSG00000249453 (HGNC:40462):

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A-AS1	XR_925475.3	n.306+288C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000249453	ENST00000506514.1	n.92+288C>T		intron_variant	Intron 1 of 2	3
PPARGC1A	ENST00000509702.5	n.2434-14756G>A		intron_variant	Intron 13 of 14	5

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18596 AN: 151940 Hom.: 1706 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0675

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.0607

Gnomad FIN AF: 0.0487

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.123 AC: 18638 AN: 152058 Hom.: 1715 Cov.: 32 AF XY: 0.120 AC XY: 8956 AN XY: 74342

African (AFR) AF: 0.250 AC: 10335 AN: 41414

American (AMR) AF: 0.154 AC: 2360 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0675 AC: 234 AN: 3468

East Asian (EAS) AF: 0.123 AC: 633 AN: 5150

South Asian (SAS) AF: 0.0607 AC: 293 AN: 4824

European-Finnish (FIN) AF: 0.0487 AC: 516 AN: 10594

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.0582 AC: 3957 AN: 68016

Other (OTH) AF: 0.112 AC: 236 AN: 2112

Alfa AF: 0.0811 Hom.: 149

Bravo AF: 0.140

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.53
PhyloP100		0.23

Splicing

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

Other links and lift over

dbSNP: rs2130925; hg19: chr4-23781592;