rs10002477

Variant names:

• chr4-23855421-G-A
• rs10002477
• NM_013261.5:c.235-23670C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-23855421-G-A
• chr4-23855421-G-C

Variant summary

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

The NM_013261.5(PPARGC1A):​c.235-23670C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,022 control chromosomes in the GnomAD database, including 32,388 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 (32388 hom., cov: 32)
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.235-23670C>T		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.235-23670C>T		intron_variant	Intron 2 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97107 AN: 151904 Hom.: 32330 Cov.: 32

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.640 AC: 97223 AN: 152022 Hom.: 32388 Cov.: 32 AF XY: 0.639 AC XY: 47483 AN XY: 74294

African (AFR) AF: 0.848 AC: 35179 AN: 41482

American (AMR) AF: 0.607 AC: 9276 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2222 AN: 3468

East Asian (EAS) AF: 0.607 AC: 3125 AN: 5152

South Asian (SAS) AF: 0.655 AC: 3154 AN: 4814

European-Finnish (FIN) AF: 0.510 AC: 5378 AN: 10550

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.540 AC: 36663 AN: 67948

Other (OTH) AF: 0.630 AC: 1332 AN: 2114

Alfa AF: 0.565 Hom.: 18152

Bravo AF: 0.655

Asia WGS AF: 0.653 AC: 2272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.32
DANN	Benign	0.47
PhyloP100		-0.57
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: rs10002477; hg19: chr4-23857044;