NM_133263.4:c.79-23051T>C

Variant names:

• chr5-149797382-T-C
• rs1012543
• NM_133263.4:c.79-23051T>C

Variant summary

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

The NM_133263.4(PPARGC1B):​c.79-23051T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,202 control chromosomes in the GnomAD database, including 4,204 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 0.22 (4204 hom., cov: 32)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133263.4. 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
	PPARGC1B	NM_133263.4	MANE Select	c.79-23051T>C		intron	N/A	NP_573570.3
	PPARGC1B	NM_001172698.2		c.79-23051T>C		intron	N/A	NP_001166169.1
	PPARGC1B	NM_001172699.2		c.4-23051T>C		intron	N/A	NP_001166170.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1B	ENST00000309241.10	TSL:1 MANE Select	c.79-23051T>C		intron	N/A	ENSP00000312649.5
	PPARGC1B	ENST00000394320.7	TSL:1	c.79-23051T>C		intron	N/A	ENSP00000377855.3
	PPARGC1B	ENST00000360453.8	TSL:1	c.79-23051T>C		intron	N/A	ENSP00000353638.4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34101 AN: 152084 Hom.: 4203 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.224 AC: 34104 AN: 152202 Hom.: 4204 Cov.: 32 AF XY: 0.223 AC XY: 16625 AN XY: 74416

African (AFR) AF: 0.129 AC: 5370 AN: 41534

American (AMR) AF: 0.233 AC: 3564 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 880 AN: 3472

East Asian (EAS) AF: 0.327 AC: 1692 AN: 5178

South Asian (SAS) AF: 0.147 AC: 708 AN: 4816

European-Finnish (FIN) AF: 0.250 AC: 2644 AN: 10586

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18271 AN: 67994

Other (OTH) AF: 0.257 AC: 544 AN: 2114

Alfa AF: 0.248 Hom.: 5094

Bravo AF: 0.221

Asia WGS AF: 0.200 AC: 697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.62
PhyloP100		1.2
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: rs1012543; hg19: chr5-149176945;