rs4619879

Variant names:

• chr4-23833253-C-A
• rs4619879
• NM_013261.5:c.235-1502G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-23833253-C-A
• chr4-23833253-C-G
• chr4-23833253-C-T

Variant summary

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

The NM_013261.5(PPARGC1A):​c.235-1502G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,034 control chromosomes in the GnomAD database, including 28,012 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 0.61 (28012 hom., cov: 33)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.663 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	NM_013261.5	MANE Select	c.235-1502G>T		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.250-1502G>T		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.250-1502G>T		intron	N/A	NP_001341754.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	ENST00000264867.7	TSL:1 MANE Select	c.235-1502G>T		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000613098.4	TSL:1	c.-147-1502G>T		intron	N/A	ENSP00000481498.1
	PPARGC1A	ENST00000506055.5	TSL:1	n.235-1502G>T		intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91935 AN: 151916 Hom.: 28004 Cov.: 33

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.605 AC: 91985 AN: 152034 Hom.: 28012 Cov.: 33 AF XY: 0.604 AC XY: 44926 AN XY: 74328

African (AFR) AF: 0.538 AC: 22331 AN: 41474

American (AMR) AF: 0.674 AC: 10294 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2234 AN: 3470

East Asian (EAS) AF: 0.512 AC: 2639 AN: 5154

South Asian (SAS) AF: 0.530 AC: 2555 AN: 4820

European-Finnish (FIN) AF: 0.643 AC: 6790 AN: 10568

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43166 AN: 67956

Other (OTH) AF: 0.624 AC: 1316 AN: 2108

Alfa AF: 0.621 Hom.: 4341

Bravo AF: 0.607

Asia WGS AF: 0.554 AC: 1926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.60
PhyloP100		-0.072
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: rs4619879; hg19: chr4-23834876;