Variant 5-149826828-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_133263.4(PPARGC1B):c.408C>G(p.Pro136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,613,936 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 3 hom. )

Consequence

PPARGC1B
NM_133263.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.86

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 5-149826828-C-G is Benign according to our data. Variant chr5-149826828-C-G is described in ClinVar as [Benign]. Clinvar id is 715843.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.86 with no splicing effect.

BS2

High AC in GnomAd4 at 221 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1B	NM_133263.4 linkuse as main transcript	c.408C>G	p.Pro136=	synonymous_variant	3/12	ENST00000309241.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1B	ENST00000309241.10 linkuse as main transcript	c.408C>G	p.Pro136=	synonymous_variant	3/12	1	NM_133263.4	P2	Q86YN6-1
PPARGC1B	ENST00000394320.7 linkuse as main transcript	c.408C>G	p.Pro136=	synonymous_variant	3/11	1		A2	Q86YN6-3
PPARGC1B	ENST00000360453.8 linkuse as main transcript	c.408C>G	p.Pro136=	synonymous_variant	3/11	1		A2	Q86YN6-5
PPARGC1B	ENST00000403750.5 linkuse as main transcript	c.333C>G	p.Pro111=	synonymous_variant	3/11	2		A2	Q86YN6-6

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

221

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00219

AC:

550

AN:

250884

Hom.:

AF XY:

0.00229

AC XY:

311

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00399

Gnomad FIN exome

AF:

0.00453

Gnomad NFE exome

AF:

0.00254

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00157

AC:

2301

AN:

1461598

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1239

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00188

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00397

Gnomad4 FIN exome

AF:

0.00489

Gnomad4 NFE exome

AF:

0.00138

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00145

AC:

221

AN:

152338

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00282

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00266

Hom.:

Bravo

AF:

0.000869

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00202

EpiControl

AF:

0.00130

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

Labcorp Genetics (formerly Invitae), Labcorp

Mar 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.6

DANN

Benign

0.49

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

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