Genetic Variant PPARGC1B:c.78+41724G>A (chr5-149772144-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

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

The NM_001172699.2(PPARGC1B):c.3+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 1,605,292 control chromosomes in the GnomAD database, including 6,197 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.081 ( 545 hom., cov: 32)

Exomes 𝑓: 0.083 ( 5652 hom. )

Consequence

PPARGC1B
NM_001172699.2 splice_region, intron

Scores

Splicing: ADA: 0.00001460

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.99

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 5-149772144-G-A is Benign according to our data. Variant chr5-149772144-G-A is described in ClinVar as [Benign]. Clinvar id is 1269772.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4 link	c.78+41724G>A		intron_variant	Intron 1 of 11	ENST00000309241.10	NP_573570.3	Q86YN6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10 link	c.78+41724G>A		intron_variant	Intron 1 of 11	1	NM_133263.4	ENSP00000312649.5		Q86YN6-1

Frequencies

GnomAD3 genomes

AF:

0.0805

AC:

12251

AN:

152158

Hom.:

545

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0657

Gnomad AMI

AF:

0.0429

Gnomad AMR

AF:

0.0578

Gnomad ASJ

AF:

0.0827

Gnomad EAS

AF:

0.0804

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.143

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0802

Gnomad OTH

AF:

0.0713

GnomAD3 exomes

AF:

0.0877

AC:

20060

AN:

228754

Hom.:

1091

AF XY:

0.0919

AC XY:

11487

AN XY:

125032

show subpopulations

Gnomad AFR exome

AF:

0.0643

Gnomad AMR exome

AF:

0.0414

Gnomad ASJ exome

AF:

0.0903

Gnomad EAS exome

AF:

0.0768

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.0771

Gnomad OTH exome

AF:

0.0935

GnomAD4 exome

AF:

0.0830

AC:

120636

AN:

1453016

Hom.:

5652

Cov.:

AF XY:

0.0858

AC XY:

61901

AN XY:

721704

show subpopulations

Gnomad4 AFR exome

AF:

0.0704

Gnomad4 AMR exome

AF:

0.0436

Gnomad4 ASJ exome

AF:

0.0919

Gnomad4 EAS exome

AF:

0.0760

Gnomad4 SAS exome

AF:

0.153

Gnomad4 FIN exome

AF:

0.149

Gnomad4 NFE exome

AF:

0.0764

Gnomad4 OTH exome

AF:

0.0854

GnomAD4 genome

AF:

0.0805

AC:

12259

AN:

152276

Hom.:

545

Cov.:

AF XY:

0.0850

AC XY:

6326

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0656

Gnomad4 AMR

AF:

0.0578

Gnomad4 ASJ

AF:

0.0827

Gnomad4 EAS

AF:

0.0808

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.143

Gnomad4 NFE

AF:

0.0802

Gnomad4 OTH

AF:

0.0729

Alfa

AF:

0.0783

Hom.:

214

Bravo

AF:

0.0704

Asia WGS

AF:

0.115

AC:

401

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.19

DANN

Benign

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000015

dbscSNV1_RF

Benign

0.0

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