NM_133263.4:c.79-18630C>T

Variant names:

• chr5-149801803-C-T
• rs4705382
• NM_133263.4:c.79-18630C>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.79-18630C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,882 control chromosomes in the GnomAD database, including 13,725 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 0.42 (13725 hom., cov: 31)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.79-18630C>T		intron_variant	Intron 1 of 11	ENST00000309241.10	NP_573570.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.79-18630C>T		intron_variant	Intron 1 of 11	1	NM_133263.4	ENSP00000312649.5

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63370 AN: 151762 Hom.: 13692 Cov.: 31

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.418 AC: 63456 AN: 151882 Hom.: 13725 Cov.: 31 AF XY: 0.416 AC XY: 30886 AN XY: 74220

African (AFR) AF: 0.491 AC: 20313 AN: 41406

American (AMR) AF: 0.543 AC: 8290 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1438 AN: 3470

East Asian (EAS) AF: 0.419 AC: 2163 AN: 5164

South Asian (SAS) AF: 0.348 AC: 1669 AN: 4802

European-Finnish (FIN) AF: 0.264 AC: 2785 AN: 10556

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.376 AC: 25536 AN: 67898

Other (OTH) AF: 0.428 AC: 904 AN: 2112

Alfa AF: 0.402 Hom.: 20219

Bravo AF: 0.447

Asia WGS AF: 0.406 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.38
PhyloP100		-0.86
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: rs4705382; hg19: chr5-149181366;