5-149826828-C-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.86

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]

ACMG classification

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 GnomAd at 221 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1B	NM_133263.4	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	c.408C>G	p.Pro136=	synonymous_variant	3/12	1	NM_133263.4	P2
PPARGC1B	ENST00000394320.7	c.408C>G	p.Pro136=	synonymous_variant	3/11	1		A2
PPARGC1B	ENST00000360453.8	c.408C>G	p.Pro136=	synonymous_variant	3/11	1		A2
PPARGC1B	ENST00000403750.5	c.333C>G	p.Pro111=	synonymous_variant	3/11	2		A2

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 221 AN: 152220 Hom.: 1 Cov.: 33

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.: 2 AF XY: 0.00229 AC XY: 311 AN XY: 135630

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.: 3 Cov.: 32 AF XY: 0.00170 AC XY: 1239 AN XY: 727130

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.: 1 Cov.: 33 AF XY: 0.00160 AC XY: 119 AN XY: 74488

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.: 0

Bravo AF: 0.000869

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00202

EpiControl AF: 0.00130

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 05, 2018

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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

Other links and lift over

dbSNP: rs147532359; hg19: chr5-149206391;