4-23874052-C-T

Variant names:

• chr4-23874052-C-T
• rs4361373
• NM_013261.5:c.234+10700G>A

Variant summary

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

The NM_013261.5(PPARGC1A):​c.234+10700G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,178 control chromosomes in the GnomAD database, including 55,038 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 0.85 (55038 hom., cov: 32)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.658
• Publications: 11 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 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+10700G>A		intron	N/A	NP_037393.1	Q9UBK2-1
	PPARGC1A	NM_001330751.2		c.249+10700G>A		intron	N/A	NP_001317680.1	Q9UBK2-3
	PPARGC1A	NM_001354825.2		c.249+10700G>A		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+10700G>A		intron	N/A	ENSP00000264867.2	Q9UBK2-1
	PPARGC1A	ENST00000613098.4	TSL:1	c.-148+6677G>A		intron	N/A	ENSP00000481498.1	Q9UBK2-9
	PPARGC1A	ENST00000506055.5	TSL:1	n.234+10700G>A		intron	N/A	ENSP00000423075.1	Q9UBK2-2

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128766 AN: 152060 Hom.: 54992 Cov.: 32

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.847 AC: 128864 AN: 152178 Hom.: 55038 Cov.: 32 AF XY: 0.840 AC XY: 62513 AN XY: 74384

African (AFR) AF: 0.939 AC: 39017 AN: 41540

American (AMR) AF: 0.718 AC: 10971 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2744 AN: 3470

East Asian (EAS) AF: 0.819 AC: 4228 AN: 5160

South Asian (SAS) AF: 0.870 AC: 4196 AN: 4822

European-Finnish (FIN) AF: 0.764 AC: 8087 AN: 10582

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56865 AN: 67998

Other (OTH) AF: 0.850 AC: 1799 AN: 2116

Alfa AF: 0.838 Hom.: 85861

Bravo AF: 0.843

Asia WGS AF: 0.856 AC: 2978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.44
PhyloP100		0.66
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: rs4361373; hg19: chr4-23875675;