rs741581

Positions:

• chr5-149823222-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133263.4(PPARGC1B):​c.252+2616G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 152,218 control chromosomes in the GnomAD database, including 366 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 0.063 (366 hom., cov: 32)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.252+2616G>A		intron_variant		ENST00000309241.10	NP_573570.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.252+2616G>A		intron_variant		1	NM_133263.4	ENSP00000312649.5
PPARGC1B	ENST00000394320.7	c.252+2616G>A		intron_variant		1		ENSP00000377855.3
PPARGC1B	ENST00000360453.8	c.252+2616G>A		intron_variant		1		ENSP00000353638.4
PPARGC1B	ENST00000403750.5	c.177+2616G>A		intron_variant		2		ENSP00000384403.1

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9596 AN: 152100 Hom.: 366 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0933

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0630 AC: 9594 AN: 152218 Hom.: 366 Cov.: 32 AF XY: 0.0600 AC XY: 4464 AN XY: 74430

Gnomad4 AFR AF: 0.0243

Gnomad4 AMR AF: 0.0685

Gnomad4 ASJ AF: 0.0798

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0234

Gnomad4 FIN AF: 0.0524

Gnomad4 NFE AF: 0.0933

Gnomad4 OTH AF: 0.0785

Alfa AF: 0.0830 Hom.: 188

Bravo AF: 0.0630

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs741581; hg19: chr5-149202785;