rs4469064

Variant names:

• chr4-23882173-A-G
• rs4469064
• NM_013261.5:c.234+2579T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_013261.5(PPARGC1A):​c.234+2579T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,178 control chromosomes in the GnomAD database, including 1,417 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 (1417 hom., cov: 33)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 14 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 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.234+2579T>C		intron	N/A	NP_037393.1	Q9UBK2-1
	PPARGC1A	NM_001330751.2		c.249+2579T>C		intron	N/A	NP_001317680.1	Q9UBK2-3
	PPARGC1A	NM_001354825.2		c.249+2579T>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.234+2579T>C		intron	N/A	ENSP00000264867.2	Q9UBK2-1
	PPARGC1A	ENST00000506055.5	TSL:1	n.234+2579T>C		intron	N/A	ENSP00000423075.1	Q9UBK2-2
	PPARGC1A	ENST00000513205.5	TSL:1	n.234+2579T>C		intron	N/A	ENSP00000421632.1	Q9UBK2-8

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18100 AN: 152050 Hom.: 1415 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0707

Gnomad ASJ AF: 0.0855

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0903

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0794

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.200 AC: 2 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.200 AC: 2 AN: 10

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.119 AC: 18127 AN: 152168 Hom.: 1417 Cov.: 33 AF XY: 0.118 AC XY: 8782 AN XY: 74410

African (AFR) AF: 0.223 AC: 9246 AN: 41492

American (AMR) AF: 0.0707 AC: 1081 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0855 AC: 297 AN: 3472

East Asian (EAS) AF: 0.108 AC: 557 AN: 5164

South Asian (SAS) AF: 0.0906 AC: 437 AN: 4822

European-Finnish (FIN) AF: 0.0732 AC: 776 AN: 10604

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0794 AC: 5400 AN: 67994

Other (OTH) AF: 0.114 AC: 240 AN: 2114

Alfa AF: 0.0877 Hom.: 1135

Bravo AF: 0.122

Asia WGS AF: 0.111 AC: 385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		-0.0060
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4469064;

hg19: chr4-23883796;