rs12500214

Variant names:

• chr4-23883945-G-A
• rs12500214
• NM_013261.5:c.234+807C>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.234+807C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,094 control chromosomes in the GnomAD database, including 2,555 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 0.16 (2555 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1A	NM_013261.5	c.234+807C>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.234+807C>T		intron_variant	Intron 2 of 12	1	NM_013261.5	ENSP00000264867.2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24972 AN: 151976 Hom.: 2557 Cov.: 33

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.191

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.164 AC: 24959 AN: 152094 Hom.: 2555 Cov.: 33 AF XY: 0.160 AC XY: 11909 AN XY: 74344

African (AFR) AF: 0.0557 AC: 2312 AN: 41540

American (AMR) AF: 0.158 AC: 2413 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 970 AN: 3472

East Asian (EAS) AF: 0.128 AC: 658 AN: 5158

South Asian (SAS) AF: 0.117 AC: 566 AN: 4826

European-Finnish (FIN) AF: 0.172 AC: 1821 AN: 10570

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.228 AC: 15484 AN: 67968

Other (OTH) AF: 0.189 AC: 399 AN: 2106

Alfa AF: 0.213 Hom.: 6240

Bravo AF: 0.162

Asia WGS AF: 0.108 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.68
PhyloP100		-0.30
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: rs12500214; hg19: chr4-23885568;