rs11746929

Variant names:

• chr5-149754311-G-A
• rs11746929
• NM_133263.4:c.78+23891G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-149754311-G-A
• chr5-149754311-G-C
• chr5-149754311-G-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.78+23891G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 134,590 control chromosomes in the GnomAD database, including 4,328 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 0.26 (4328 hom., cov: 30)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.78+23891G>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+23891G>A		intron_variant	Intron 1 of 11	1	NM_133263.4	ENSP00000312649.5
PPARGC1B	ENST00000394320.7	c.78+23891G>A		intron_variant	Intron 1 of 10	1		ENSP00000377855.3
PPARGC1B	ENST00000360453.8	c.78+23891G>A		intron_variant	Intron 1 of 10	1		ENSP00000353638.4
PPARGC1B	ENST00000461780.1	n.252-7121G>A		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.259 AC: 34847 AN: 134484 Hom.: 4322 Cov.: 30

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.259 AC: 34864 AN: 134590 Hom.: 4328 Cov.: 30 AF XY: 0.263 AC XY: 17210 AN XY: 65328

African (AFR) AF: 0.166 AC: 6288 AN: 37918

American (AMR) AF: 0.381 AC: 5398 AN: 14170

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 809 AN: 3056

East Asian (EAS) AF: 0.381 AC: 1763 AN: 4630

South Asian (SAS) AF: 0.380 AC: 1538 AN: 4050

European-Finnish (FIN) AF: 0.253 AC: 2117 AN: 8364

Middle Eastern (MID) AF: 0.267 AC: 71 AN: 266

European-Non Finnish (NFE) AF: 0.272 AC: 16152 AN: 59418

Other (OTH) AF: 0.285 AC: 535 AN: 1878

Alfa AF: 0.303 Hom.: 11068

Bravo AF: 0.242

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.53
PhyloP100		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=18/82	disease causing

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: rs11746929; hg19: chr5-149133874; COSMIC: COSV58527571;