rs6892794

Variant names:

• chr5-149744568-A-G
• rs6892794
• NM_133263.4:c.78+14148A>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.78+14148A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,112 control chromosomes in the GnomAD database, including 8,240 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 0.32 (8240 hom., cov: 32)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• Publications: 7 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.78+14148A>G		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+14148A>G		intron_variant	Intron 1 of 11	1	NM_133263.4	ENSP00000312649.5
PPARGC1B	ENST00000394320.7	c.78+14148A>G		intron_variant	Intron 1 of 10	1		ENSP00000377855.3
PPARGC1B	ENST00000360453.8	c.78+14148A>G		intron_variant	Intron 1 of 10	1		ENSP00000353638.4
PPARGC1B	ENST00000461780.1	n.251+4443A>G		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47923 AN: 151996 Hom.: 8216 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.316 AC: 47992 AN: 152112 Hom.: 8240 Cov.: 32 AF XY: 0.316 AC XY: 23514 AN XY: 74358

African (AFR) AF: 0.450 AC: 18670 AN: 41454

American (AMR) AF: 0.242 AC: 3698 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 771 AN: 3472

East Asian (EAS) AF: 0.410 AC: 2127 AN: 5182

South Asian (SAS) AF: 0.353 AC: 1695 AN: 4804

European-Finnish (FIN) AF: 0.248 AC: 2622 AN: 10588

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17539 AN: 67998

Other (OTH) AF: 0.307 AC: 648 AN: 2114

Alfa AF: 0.279 Hom.: 3577

Bravo AF: 0.318

Asia WGS AF: 0.413 AC: 1432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.6
DANN	Benign	0.79
PhyloP100		-0.77
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: rs6892794; hg19: chr5-149124131; COSMIC: COSV58527543;