4-23861310-A-T

Variant names:

• chr4-23861310-A-T
• rs11724368
• NM_013261.5:c.234+23442T>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+23442T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,228 control chromosomes in the GnomAD database, including 3,569 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 0.20 (3569 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• 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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.234+23442T>A		intron_variant	Intron 2 of 12	ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.234+23442T>A		intron_variant	Intron 2 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30915 AN: 152110 Hom.: 3555 Cov.: 33

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.203 AC: 30947 AN: 152228 Hom.: 3569 Cov.: 33 AF XY: 0.209 AC XY: 15564 AN XY: 74430

African (AFR) AF: 0.0854 AC: 3550 AN: 41562

American (AMR) AF: 0.258 AC: 3948 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 847 AN: 3466

East Asian (EAS) AF: 0.308 AC: 1595 AN: 5176

South Asian (SAS) AF: 0.321 AC: 1549 AN: 4822

European-Finnish (FIN) AF: 0.279 AC: 2957 AN: 10604

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15773 AN: 67996

Other (OTH) AF: 0.220 AC: 464 AN: 2112

Alfa AF: 0.118 Hom.: 203

Bravo AF: 0.194

Asia WGS AF: 0.348 AC: 1211 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.8
DANN	Benign	0.69
PhyloP100		0.029
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: rs11724368; hg19: chr4-23862933;