4-23867831-C-T

Variant names:

• chr4-23867831-C-T
• rs7677000
• NM_013261.5:c.234+16921G>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+16921G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,174 control chromosomes in the GnomAD database, including 3,157 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 0.19 (3157 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383
• Publications: 8 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 (AFR) allele frequency at 95% confidence interval = 0.27 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+16921G>A		intron	N/A	NP_037393.1	Q9UBK2-1
	PPARGC1A	NM_001330751.2		c.249+16921G>A		intron	N/A	NP_001317680.1	Q9UBK2-3
	PPARGC1A	NM_001354825.2		c.249+16921G>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+16921G>A		intron	N/A	ENSP00000264867.2	Q9UBK2-1
	PPARGC1A	ENST00000613098.4	TSL:1	c.-148+12898G>A		intron	N/A	ENSP00000481498.1	Q9UBK2-9
	PPARGC1A	ENST00000506055.5	TSL:1	n.234+16921G>A		intron	N/A	ENSP00000423075.1	Q9UBK2-2

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29609 AN: 152056 Hom.: 3151 Cov.: 33

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.195 AC: 29648 AN: 152174 Hom.: 3157 Cov.: 33 AF XY: 0.194 AC XY: 14464 AN XY: 74406

African (AFR) AF: 0.274 AC: 11380 AN: 41470

American (AMR) AF: 0.217 AC: 3322 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 605 AN: 3472

East Asian (EAS) AF: 0.153 AC: 793 AN: 5182

South Asian (SAS) AF: 0.187 AC: 903 AN: 4830

European-Finnish (FIN) AF: 0.140 AC: 1483 AN: 10592

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10584 AN: 68014

Other (OTH) AF: 0.188 AC: 397 AN: 2112

Alfa AF: 0.177 Hom.: 947

Bravo AF: 0.207

Asia WGS AF: 0.164 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.74
PhyloP100		0.38
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: rs7677000; hg19: chr4-23869454;