NM_133263.4:c.252+751A>G

Variant names:

• chr5-149821357-A-G
• rs32586
• NM_133263.4:c.252+751A>G

Variant summary

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

The NM_133263.4(PPARGC1B):​c.252+751A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,086 control chromosomes in the GnomAD database, including 3,130 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 0.19 (3130 hom., cov: 32)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65
• Publications: 3 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.252+751A>G		intron_variant	Intron 2 of 11	ENST00000309241.10	NP_573570.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.252+751A>G		intron_variant	Intron 2 of 11	1	NM_133263.4	ENSP00000312649.5
PPARGC1B	ENST00000394320.7	c.252+751A>G		intron_variant	Intron 2 of 10	1		ENSP00000377855.3
PPARGC1B	ENST00000360453.8	c.252+751A>G		intron_variant	Intron 2 of 10	1		ENSP00000353638.4
PPARGC1B	ENST00000403750.5	c.177+751A>G		intron_variant	Intron 2 of 10	2		ENSP00000384403.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28226 AN: 151968 Hom.: 3120 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0763

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.186 AC: 28250 AN: 152086 Hom.: 3130 Cov.: 32 AF XY: 0.190 AC XY: 14101 AN XY: 74328

African (AFR) AF: 0.296 AC: 12276 AN: 41478

American (AMR) AF: 0.110 AC: 1685 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3470

East Asian (EAS) AF: 0.0765 AC: 395 AN: 5166

South Asian (SAS) AF: 0.212 AC: 1019 AN: 4806

European-Finnish (FIN) AF: 0.253 AC: 2678 AN: 10568

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9134 AN: 67986

Other (OTH) AF: 0.158 AC: 333 AN: 2114

Alfa AF: 0.171 Hom.: 320

Bravo AF: 0.175

Asia WGS AF: 0.141 AC: 489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		2.7
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: rs32586; hg19: chr5-149200920;