Variant rs32577 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.1164G>A(p.Pro388Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,613,216 control chromosomes in the GnomAD database, including 18,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2232 hom., cov: 33)

Exomes 𝑓: 0.14 ( 15782 hom. )

Consequence

PPARGC1B
NM_133263.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.54

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=-0.95).

BP6

Variant 5-149833237-G-A is Benign according to our data. Variant chr5-149833237-G-A is described in ClinVar as [Benign]. Clinvar id is 1276406.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 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.1164G>A	p.Pro388Pro	synonymous_variant	5/12	ENST00000309241.10	NP_573570.3	Q86YN6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10 linkuse as main transcript	c.1164G>A	p.Pro388Pro	synonymous_variant	5/12	1	NM_133263.4	ENSP00000312649.5		Q86YN6-1

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24861

AN:

152096

Hom.:

2227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.0983

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.0129

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.140

GnomAD3 exomes

AF:

0.146

AC:

36567

AN:

249672

Hom.:

3235

AF XY:

0.153

AC XY:

20687

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.0708

Gnomad ASJ exome

AF:

0.164

Gnomad EAS exome

AF:

0.00555

Gnomad SAS exome

AF:

0.224

Gnomad FIN exome

AF:

0.244

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.139

AC:

203136

AN:

1461004

Hom.:

15782

Cov.:

AF XY:

0.143

AC XY:

103731

AN XY:

726798

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.0744

Gnomad4 ASJ exome

AF:

0.163

Gnomad4 EAS exome

AF:

0.0261

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.242

Gnomad4 NFE exome

AF:

0.131

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

AF:

0.164

AC:

24888

AN:

152212

Hom.:

2232

Cov.:

AF XY:

0.169

AC XY:

12571

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.0981

Gnomad4 ASJ

AF:

0.164

Gnomad4 EAS

AF:

0.0129

Gnomad4 SAS

AF:

0.216

Gnomad4 FIN

AF:

0.262

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.139

Alfa

AF:

0.145

Hom.:

1232

Bravo

AF:

0.150

Asia WGS

AF:

0.121

AC:

422

AN:

3478

EpiCase

AF:

0.135

EpiControl

AF:

0.134

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

-0.95

CADD

Benign

0.089

DANN

Benign

0.57

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