5-149820445-G-A

Position:

chr5-149820445-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_133263.4(PPARGC1B):c.91G>A(p.Gly31Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,718 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 12 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 13 hom. )

Consequence

PPARGC1B
NM_133263.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.42

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=0.00728783).

BP6

Variant 5-149820445-G-A is Benign according to our data. Variant chr5-149820445-G-A is described in ClinVar as [Benign]. Clinvar id is 780570.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00624 (950/152222) while in subpopulation AFR AF= 0.0217 (902/41536). AF 95% confidence interval is 0.0205. There are 12 homozygotes in gnomad4. There are 472 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 950 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1B	NM_133263.4 linkuse as main transcript	c.91G>A	p.Gly31Arg	missense_variant	2/12	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.91G>A	p.Gly31Arg	missense_variant	2/12	1	NM_133263.4	ENSP00000312649	P2	Q86YN6-1
PPARGC1B	ENST00000394320.7 linkuse as main transcript	c.91G>A	p.Gly31Arg	missense_variant	2/11	1		ENSP00000377855	A2	Q86YN6-3
PPARGC1B	ENST00000360453.8 linkuse as main transcript	c.91G>A	p.Gly31Arg	missense_variant	2/11	1		ENSP00000353638	A2	Q86YN6-5
PPARGC1B	ENST00000403750.5 linkuse as main transcript	c.16G>A	p.Gly6Arg	missense_variant	2/11	2		ENSP00000384403	A2	Q86YN6-6

Frequencies

GnomAD3 genomes

AF:

0.00621

AC:

944

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0216

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00167

AC:

418

AN:

251014

Hom.:

AF XY:

0.00119

AC XY:

162

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.0225

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.000675

AC:

987

AN:

1461496

Hom.:

Cov.:

AF XY:

0.000598

AC XY:

435

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.0213

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.00624

AC:

950

AN:

152222

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

472

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0217

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.00739

ESP6500AA

AF:

0.0218

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00213

AC:

258

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

.;.;T;.

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

D;T;T;T

MetaRNN

Benign

0.0073

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.39

MutPred

0.32

Loss of glycosylation at S30 (P = 0.038);Loss of glycosylation at S30 (P = 0.038);Loss of glycosylation at S30 (P = 0.038);.;

MVP

0.36

MPC

0.68

ClinPred

0.033

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.45

gMVP

0.32

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