4-23834777-C-T

Variant names:

• chr4-23834777-C-T
• rs4697046
• NM_013261.5:c.235-3026G>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.235-3026G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 151,904 control chromosomes in the GnomAD database, including 30,945 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 0.64 (30945 hom., cov: 31)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.686 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.235-3026G>A		intron	N/A	NP_037393.1	Q9UBK2-1
	PPARGC1A	NM_001330751.2		c.250-3026G>A		intron	N/A	NP_001317680.1	Q9UBK2-3
	PPARGC1A	NM_001354825.2		c.250-3026G>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.235-3026G>A		intron	N/A	ENSP00000264867.2	Q9UBK2-1
	PPARGC1A	ENST00000613098.4	TSL:1	c.-147-3026G>A		intron	N/A	ENSP00000481498.1	Q9UBK2-9
	PPARGC1A	ENST00000506055.5	TSL:1	n.235-3026G>A		intron	N/A	ENSP00000423075.1	Q9UBK2-2

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96866 AN: 151786 Hom.: 30915 Cov.: 31

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.638 AC: 96949 AN: 151904 Hom.: 30945 Cov.: 31 AF XY: 0.637 AC XY: 47291 AN XY: 74206

African (AFR) AF: 0.610 AC: 25273 AN: 41414

American (AMR) AF: 0.697 AC: 10653 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2338 AN: 3466

East Asian (EAS) AF: 0.520 AC: 2683 AN: 5160

South Asian (SAS) AF: 0.601 AC: 2895 AN: 4814

European-Finnish (FIN) AF: 0.647 AC: 6799 AN: 10514

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44179 AN: 67940

Other (OTH) AF: 0.659 AC: 1391 AN: 2112

Alfa AF: 0.655 Hom.: 4049

Bravo AF: 0.641

Asia WGS AF: 0.615 AC: 2138 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.49
PhyloP100		0.53
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: rs4697046;

hg19: chr4-23836400;