rs880770

Variant names:

• chr5-149775272-G-A
• rs880770
• NM_133263.4:c.78+44852G>A

Variant summary

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

The NM_133263.4(PPARGC1B):​c.78+44852G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,018 control chromosomes in the GnomAD database, including 28,961 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 0.61 (28961 hom., cov: 32)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.78+44852G>A		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.78+44852G>A		intron_variant	Intron 1 of 11	1	NM_133263.4	ENSP00000312649.5

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93309 AN: 151900 Hom.: 28944 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.614 AC: 93367 AN: 152018 Hom.: 28961 Cov.: 32 AF XY: 0.614 AC XY: 45634 AN XY: 74282

African (AFR) AF: 0.547 AC: 22677 AN: 41448

American (AMR) AF: 0.670 AC: 10247 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2048 AN: 3472

East Asian (EAS) AF: 0.782 AC: 4044 AN: 5174

South Asian (SAS) AF: 0.659 AC: 3177 AN: 4824

European-Finnish (FIN) AF: 0.572 AC: 6034 AN: 10544

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 42979 AN: 67948

Other (OTH) AF: 0.666 AC: 1410 AN: 2116

Alfa AF: 0.629 Hom.: 16207

Bravo AF: 0.621

Asia WGS AF: 0.694 AC: 2410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.70
DANN	Benign	0.43
PhyloP100		-0.91
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: rs880770; hg19: chr5-149154835;