NM_013261.5:c.877+2384T>C

Variant names:

• chr4-23821896-A-G
• rs2970853
• NM_013261.5:c.877+2384T>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.877+2384T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 151,828 control chromosomes in the GnomAD database, including 42,008 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 0.74 (42008 hom., cov: 31)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013261.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	NM_013261.5	MANE Select	c.877+2384T>C		intron	N/A	NP_037393.1	Q9UBK2-1
	PPARGC1A	NM_001330751.2		c.892+2384T>C		intron	N/A	NP_001317680.1	Q9UBK2-3
	PPARGC1A	NM_001354825.2		c.892+2384T>C		intron	N/A	NP_001341754.1	Q9UBK2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	ENST00000264867.7	TSL:1 MANE Select	c.877+2384T>C		intron	N/A	ENSP00000264867.2	Q9UBK2-1
	PPARGC1A	ENST00000613098.4	TSL:1	c.496+2384T>C		intron	N/A	ENSP00000481498.1	Q9UBK2-9
	PPARGC1A	ENST00000506055.5	TSL:1	n.*92+2384T>C		intron	N/A	ENSP00000423075.1	Q9UBK2-2

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112660 AN: 151710 Hom.: 41976 Cov.: 31

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.743 AC: 112744 AN: 151828 Hom.: 42008 Cov.: 31 AF XY: 0.747 AC XY: 55437 AN XY: 74188

African (AFR) AF: 0.701 AC: 29040 AN: 41422

American (AMR) AF: 0.812 AC: 12361 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2742 AN: 3464

East Asian (EAS) AF: 0.711 AC: 3648 AN: 5132

South Asian (SAS) AF: 0.773 AC: 3728 AN: 4820

European-Finnish (FIN) AF: 0.802 AC: 8463 AN: 10554

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50257 AN: 67892

Other (OTH) AF: 0.768 AC: 1618 AN: 2108

Alfa AF: 0.744 Hom.: 68591

Bravo AF: 0.739

Asia WGS AF: 0.771 AC: 2681 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.57
PhyloP100		-0.63
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: rs2970853; hg19: chr4-23823519;