NM_013261.5:c.2020-1518T>C

Variant names:

• chr4-23803863-A-G
• rs2932965
• NM_013261.5:c.2020-1518T>C

Variant summary

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

The NM_013261.5(PPARGC1A):​c.2020-1518T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,116 control chromosomes in the GnomAD database, including 50,488 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 0.81 (50488 hom., cov: 31)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 10 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.2020-1518T>C		intron_variant	Intron 10 of 12	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.2020-1518T>C		intron_variant	Intron 10 of 12	1	NM_013261.5	ENSP00000264867.2
PPARGC1A	ENST00000613098.4	c.1639-1518T>C		intron_variant	Intron 9 of 11	1		ENSP00000481498.1
PPARGC1A	ENST00000506055.5	n.*1235-1518T>C		intron_variant	Intron 10 of 12	1		ENSP00000423075.1
PPARGC1A	ENST00000509702.5	n.2060-1518T>C		intron_variant	Intron 10 of 14	5

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123652 AN: 151998 Hom.: 50439 Cov.: 31

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.832

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

GnomAD4 genome AF: 0.814 AC: 123761 AN: 152116 Hom.: 50488 Cov.: 31 AF XY: 0.817 AC XY: 60724 AN XY: 74336

African (AFR) AF: 0.850 AC: 35308 AN: 41522

American (AMR) AF: 0.859 AC: 13128 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 2963 AN: 3470

East Asian (EAS) AF: 0.772 AC: 3972 AN: 5146

South Asian (SAS) AF: 0.839 AC: 4047 AN: 4822

European-Finnish (FIN) AF: 0.816 AC: 8627 AN: 10572

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53026 AN: 67982

Other (OTH) AF: 0.834 AC: 1761 AN: 2112

Alfa AF: 0.791 Hom.: 200485

Bravo AF: 0.818

Asia WGS AF: 0.841 AC: 2925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.4
DANN	Benign	0.42
PhyloP100		0.010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2932965; hg19: chr4-23805486;