4-23815404-A-G

Variant names:

• chr4-23815404-A-G
• rs2970848
• NM_013261.5:c.878-799T>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.878-799T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,898 control chromosomes in the GnomAD database, including 12,008 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 0.39 (12008 hom., cov: 31)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417
• Publications: 22 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.478 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.878-799T>C		intron	N/A	NP_037393.1	Q9UBK2-1
	PPARGC1A	NM_001330751.2		c.893-799T>C		intron	N/A	NP_001317680.1	Q9UBK2-3
	PPARGC1A	NM_001354825.2		c.893-799T>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.878-799T>C		intron	N/A	ENSP00000264867.2	Q9UBK2-1
	PPARGC1A	ENST00000613098.4	TSL:1	c.497-799T>C		intron	N/A	ENSP00000481498.1	Q9UBK2-9
	PPARGC1A	ENST00000506055.5	TSL:1	n.*93-799T>C		intron	N/A	ENSP00000423075.1	Q9UBK2-2

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58746 AN: 151780 Hom.: 11991 Cov.: 31

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.387 AC: 58820 AN: 151898 Hom.: 12008 Cov.: 31 AF XY: 0.394 AC XY: 29274 AN XY: 74228

African (AFR) AF: 0.483 AC: 20014 AN: 41420

American (AMR) AF: 0.448 AC: 6838 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 970 AN: 3466

East Asian (EAS) AF: 0.267 AC: 1371 AN: 5142

South Asian (SAS) AF: 0.358 AC: 1731 AN: 4830

European-Finnish (FIN) AF: 0.442 AC: 4650 AN: 10532

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22028 AN: 67946

Other (OTH) AF: 0.363 AC: 766 AN: 2108

Alfa AF: 0.337 Hom.: 26985

Bravo AF: 0.388

Asia WGS AF: 0.345 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.45
DANN	Benign	0.40
PhyloP100		-0.42
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: rs2970848; hg19: chr4-23817027;