5-149820480-T-C

Variant names:

• chr5-149820480-T-C
• rs32588
• NM_133263.4:c.126T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_133263.4(PPARGC1B):​c.126T>C​(p.Leu42Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,744 control chromosomes in the GnomAD database, including 20,157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3799 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16358 hom.)
• Consequence: PPARGC1B NM_133263.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-149820480-T-C is Benign according to our data. Variant chr5-149820480-T-C is described in ClinVar as [Benign]. Clinvar id is 1253494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.9 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.126T>C	p.Leu42Leu	synonymous_variant	Exon 2 of 12	ENST00000309241.10	NP_573570.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.126T>C	p.Leu42Leu	synonymous_variant	Exon 2 of 12	1	NM_133263.4	ENSP00000312649.5
PPARGC1B	ENST00000394320.7	c.126T>C	p.Leu42Leu	synonymous_variant	Exon 2 of 11	1		ENSP00000377855.3
PPARGC1B	ENST00000360453.8	c.126T>C	p.Leu42Leu	synonymous_variant	Exon 2 of 11	1		ENSP00000353638.4
PPARGC1B	ENST00000403750.5	c.51T>C	p.Leu17Leu	synonymous_variant	Exon 2 of 11	2		ENSP00000384403.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30383 AN: 151934 Hom.: 3786 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0755

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.166

GnomAD2 exomes AF: 0.157 AC: 39508 AN: 251270 AF XY: 0.160

Gnomad AFR exome AF: 0.350

Gnomad AMR exome AF: 0.0769

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.0783

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.139 AC: 203310 AN: 1461692 Hom.: 16358 Cov.: 32 AF XY: 0.142 AC XY: 103406 AN XY: 727166

African (AFR) AF: 0.358 AC: 11981 AN: 33476

American (AMR) AF: 0.0812 AC: 3630 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 4152 AN: 26136

East Asian (EAS) AF: 0.0749 AC: 2974 AN: 39700

South Asian (SAS) AF: 0.220 AC: 18954 AN: 86256

European-Finnish (FIN) AF: 0.233 AC: 12441 AN: 53306

Middle Eastern (MID) AF: 0.176 AC: 1017 AN: 5766

European-Non Finnish (NFE) AF: 0.125 AC: 139329 AN: 1111936

Other (OTH) AF: 0.146 AC: 8832 AN: 60392

GnomAD4 genome AF: 0.200 AC: 30421 AN: 152052 Hom.: 3799 Cov.: 32 AF XY: 0.204 AC XY: 15146 AN XY: 74312

African (AFR) AF: 0.345 AC: 14322 AN: 41454

American (AMR) AF: 0.116 AC: 1780 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3468

East Asian (EAS) AF: 0.0757 AC: 391 AN: 5166

South Asian (SAS) AF: 0.211 AC: 1015 AN: 4800

European-Finnish (FIN) AF: 0.253 AC: 2676 AN: 10576

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9151 AN: 67984

Other (OTH) AF: 0.167 AC: 352 AN: 2114

Alfa AF: 0.150 Hom.: 6893

Bravo AF: 0.192

Asia WGS AF: 0.144 AC: 500 AN: 3478

EpiCase AF: 0.130

EpiControl AF: 0.129

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.37
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs32588; hg19: chr5-149200043; COSMIC: COSV58527409; COSMIC: COSV58527409;