4-23809024-C-T

Position:

• chr4-23809024-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000264867.7(PPARGC1A):​c.2019+3723G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,572 control chromosomes in the GnomAD database, including 23,232 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 0.55 (23232 hom., cov: 30)
• Consequence: PPARGC1A ENST00000264867.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.2019+3723G>A		intron_variant		ENST00000264867.7	NP_037393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1A	ENST00000264867.7	c.2019+3723G>A		intron_variant		1	NM_013261.5	ENSP00000264867	P1
PPARGC1A	ENST00000613098.4	c.1638+3723G>A		intron_variant		1		ENSP00000481498
PPARGC1A	ENST00000506055.5	c.*1234+3723G>A		intron_variant, NMD_transcript_variant		1		ENSP00000423075
PPARGC1A	ENST00000509702.5	n.2059+3723G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83161 AN: 151454 Hom.: 23220 Cov.: 30

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.549 AC: 83221 AN: 151572 Hom.: 23232 Cov.: 30 AF XY: 0.550 AC XY: 40680 AN XY: 74002

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.584

Alfa AF: 0.526 Hom.: 9737

Bravo AF: 0.556

Asia WGS AF: 0.655 AC: 2268 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.60
DANN	Benign	0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs3774921; hg19: chr4-23810647;