Variant 5-149820480-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_133263.4(PPARGC1B):c.126T>C(p.Leu42Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,744 control chromosomes in the GnomAD database, including 20,157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3799 hom., cov: 32)

Exomes 𝑓: 0.14 ( 16358 hom. )

Consequence

PPARGC1B
NM_133263.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.90

Variant links:

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]

PPARGC1B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 5-149820480-T-C is Benign according to our data. Variant chr5-149820480-T-C is described in ClinVar as [Benign]. Clinvar id is 1253494.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.9 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1B	NM_133263.4 linkuse as main transcript	c.126T>C	p.Leu42Leu	synonymous_variant	2/12	ENST00000309241.10	NP_573570.3	Q86YN6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PPARGC1B	ENST00000309241.10 linkuse as main transcript	c.126T>C	p.Leu42Leu	synonymous_variant	2/12	1	NM_133263.4	ENSP00000312649.5	Q86YN6-1
PPARGC1B	ENST00000394320.7 linkuse as main transcript	c.126T>C	p.Leu42Leu	synonymous_variant	2/11	1		ENSP00000377855.3	Q86YN6-3
PPARGC1B	ENST00000360453.8 linkuse as main transcript	c.126T>C	p.Leu42Leu	synonymous_variant	2/11	1		ENSP00000353638.4	Q86YN6-5
PPARGC1B	ENST00000403750.5 linkuse as main transcript	c.51T>C	p.Leu17Leu	synonymous_variant	2/11	2		ENSP00000384403.1	Q86YN6-6

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30383

AN:

151934

Hom.:

3786

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.0755

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.166

GnomAD3 exomes

AF:

0.157

AC:

39508

AN:

251270

Hom.:

3809

AF XY:

0.160

AC XY:

21684

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.350

Gnomad AMR exome

AF:

0.0769

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.0783

Gnomad SAS exome

AF:

0.219

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.139

AC:

203310

AN:

1461692

Hom.:

16358

Cov.:

AF XY:

0.142

AC XY:

103406

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.358

Gnomad4 AMR exome

AF:

0.0812

Gnomad4 ASJ exome

AF:

0.159

Gnomad4 EAS exome

AF:

0.0749

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.233

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.146

GnomAD4 genome

AF:

0.200

AC:

30421

AN:

152052

Hom.:

3799

Cov.:

AF XY:

0.204

AC XY:

15146

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.345

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.160

Gnomad4 EAS

AF:

0.0757

Gnomad4 SAS

AF:

0.211

Gnomad4 FIN

AF:

0.253

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.138

Hom.:

3541

Bravo

AF:

0.192

Asia WGS

AF:

0.144

AC:

500

AN:

3478

EpiCase

AF:

0.130

EpiControl

AF:

0.129

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.54

DANN

Benign

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over