rs32579

Variant names:

• chr5-149831285-C-T
• rs32579
• NM_133263.4:c.582+402C>T

Variant summary

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

The NM_133263.4(PPARGC1B):​c.582+402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,000 control chromosomes in the GnomAD database, including 12,012 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 0.38 (12012 hom., cov: 32)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999
• Publications: 29 publications found

Genes affected

PPARGC1B (HGNC:30022): (PPARG coactivator 1 beta) The protein encoded by this gene stimulates the activity of several transcription factors and nuclear receptors, including estrogen receptor alpha, nuclear respiratory factor 1, and glucocorticoid receptor. The encoded protein may be involved in fat oxidation, non-oxidative glucose metabolism, and the regulation of energy expenditure. This protein is downregulated in prediabetic and type 2 diabetes mellitus patients. Certain allelic variations in this gene increase the risk of the development of obesity. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.582+402C>T		intron_variant	Intron 4 of 11	ENST00000309241.10	NP_573570.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.582+402C>T		intron_variant	Intron 4 of 11	1	NM_133263.4	ENSP00000312649.5
PPARGC1B	ENST00000394320.7	c.582+402C>T		intron_variant	Intron 4 of 10	1		ENSP00000377855.3
PPARGC1B	ENST00000360453.8	c.466-1371C>T		intron_variant	Intron 3 of 10	1		ENSP00000353638.4
PPARGC1B	ENST00000403750.5	c.391-1371C>T		intron_variant	Intron 3 of 10	2		ENSP00000384403.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58349 AN: 151880 Hom.: 11991 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.384 AC: 58425 AN: 152000 Hom.: 12012 Cov.: 32 AF XY: 0.391 AC XY: 29070 AN XY: 74288

African (AFR) AF: 0.520 AC: 21542 AN: 41454

American (AMR) AF: 0.449 AC: 6849 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3466

East Asian (EAS) AF: 0.348 AC: 1795 AN: 5154

South Asian (SAS) AF: 0.390 AC: 1876 AN: 4816

European-Finnish (FIN) AF: 0.384 AC: 4058 AN: 10558

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 20004 AN: 67964

Other (OTH) AF: 0.371 AC: 784 AN: 2114

Alfa AF: 0.324 Hom.: 29637

Bravo AF: 0.397

Asia WGS AF: 0.357 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.49
DANN	Benign	0.33
PhyloP100		-1.0
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: rs32579; hg19: chr5-149210848;