Variant chr5-149832680-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000309241.10(PPARGC1B):c.607G>C(p.Ala203Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 1,547,582 control chromosomes in the GnomAD database, including 6,416 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1015 hom., cov: 32)

Exomes 𝑓: 0.085 ( 5401 hom. )

Consequence

PPARGC1B
ENST00000309241.10 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.132

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012690127).

BP6

Variant 5-149832680-G-C is Benign according to our data. Variant chr5-149832680-G-C is described in ClinVar as [Benign]. Clinvar id is 2039.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.158 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.607G>C	p.Ala203Pro	missense_variant	5/12	ENST00000309241.10	NP_573570.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10 linkuse as main transcript	c.607G>C	p.Ala203Pro	missense_variant	5/12	1	NM_133263.4	ENSP00000312649	P2	Q86YN6-1
PPARGC1B	ENST00000394320.7 linkuse as main transcript	c.607G>C	p.Ala203Pro	missense_variant	5/11	1		ENSP00000377855	A2	Q86YN6-3
PPARGC1B	ENST00000360453.8 linkuse as main transcript	c.490G>C	p.Ala164Pro	missense_variant	4/11	1		ENSP00000353638	A2	Q86YN6-5
PPARGC1B	ENST00000403750.5 linkuse as main transcript	c.415G>C	p.Ala139Pro	missense_variant	4/11	2		ENSP00000384403	A2	Q86YN6-6

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16510

AN:

152060

Hom.:

1009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.0824

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.0597

Gnomad SAS

AF:

0.0617

Gnomad FIN

AF:

0.0462

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0804

Gnomad OTH

AF:

0.117

GnomAD3 exomes

AF:

0.0939

AC:

19531

AN:

207962

Hom.:

1122

AF XY:

0.0905

AC XY:

10043

AN XY:

110986

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.0640

Gnomad SAS exome

AF:

0.0668

Gnomad FIN exome

AF:

0.0487

Gnomad NFE exome

AF:

0.0836

Gnomad OTH exome

AF:

0.0859

GnomAD4 exome

AF:

0.0848

AC:

118292

AN:

1395404

Hom.:

5401

Cov.:

AF XY:

0.0840

AC XY:

57570

AN XY:

685398

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.0580

Gnomad4 SAS exome

AF:

0.0651

Gnomad4 FIN exome

AF:

0.0498

Gnomad4 NFE exome

AF:

0.0825

Gnomad4 OTH exome

AF:

0.0924

GnomAD4 genome

AF:

0.109

AC:

16545

AN:

152178

Hom.:

1015

Cov.:

AF XY:

0.109

AC XY:

8134

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.0598

Gnomad4 SAS

AF:

0.0613

Gnomad4 FIN

AF:

0.0462

Gnomad4 NFE

AF:

0.0804

Gnomad4 OTH

AF:

0.116

Alfa

AF:

0.0910

Hom.:

476

Bravo

AF:

0.119

TwinsUK

AF:

0.0774

AC:

287

ALSPAC

AF:

0.0825

AC:

318

ESP6500AA

AF:

0.161

AC:

708

ESP6500EA

AF:

0.0841

AC:

723

ExAC

AF:

0.0916

AC:

11106

Asia WGS

AF:

0.0580

AC:

202

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

This variant is associated with the following publications: (PMID: 15863669, 19653005, 16704985) -

PPARGC1B polymorphism

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

May 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.4

DANN

Benign

0.19

DEOGEN2

Benign

0.083

.;.;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.51

T;T;T;T

MetaRNN

Benign

0.0013

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

.;L;L;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.030

N;N;N;N

REVEL

Benign

0.023

Sift

Benign

0.39

T;T;T;T

Sift4G

Benign

0.39

T;T;T;T

Polyphen

0.0030

B;B;B;.

Vest4

0.10

MPC

0.21

ClinPred

0.0026

GERP RS

-4.3

Varity_R

0.050

gMVP

0.073

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