chr5-149786871-C-T

Variant names:

• chr5-149786871-C-T
• rs1422429
• NM_133263.4:c.79-33562C>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.79-33562C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,022 control chromosomes in the GnomAD database, including 15,473 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 0.45 (15473 hom., cov: 32)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.79-33562C>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.79-33562C>T		intron_variant	Intron 1 of 11	1	NM_133263.4	ENSP00000312649.5

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67995 AN: 151904 Hom.: 15462 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.448 AC: 68045 AN: 152022 Hom.: 15473 Cov.: 32 AF XY: 0.446 AC XY: 33163 AN XY: 74290

African (AFR) AF: 0.469 AC: 19440 AN: 41436

American (AMR) AF: 0.406 AC: 6212 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1386 AN: 3470

East Asian (EAS) AF: 0.698 AC: 3613 AN: 5174

South Asian (SAS) AF: 0.435 AC: 2096 AN: 4814

European-Finnish (FIN) AF: 0.365 AC: 3854 AN: 10556

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29904 AN: 67966

Other (OTH) AF: 0.458 AC: 966 AN: 2110

Alfa AF: 0.439 Hom.: 42065

Bravo AF: 0.449

Asia WGS AF: 0.529 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.81
PhyloP100		0.22
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: rs1422429; hg19: chr5-149166434; COSMIC: COSV58527706;