chr5-149826541-G-A

Position:

• chr5-149826541-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_133263.4(PPARGC1B):​c.253-132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 692,006 control chromosomes in the GnomAD database, including 1,156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.059 (391 hom., cov: 33)
  • Exomes 𝑓: 0.041 (765 hom.)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.379

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-149826541-G-A is Benign according to our data. Variant chr5-149826541-G-A is described in ClinVar as [Benign]. Clinvar id is 1237166.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.253-132G>A		intron_variant		ENST00000309241.10	NP_573570.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.253-132G>A		intron_variant		1	NM_133263.4	ENSP00000312649	P2
PPARGC1B	ENST00000360453.8	c.253-132G>A		intron_variant		1		ENSP00000353638	A2
PPARGC1B	ENST00000394320.7	c.253-132G>A		intron_variant		1		ENSP00000377855	A2
PPARGC1B	ENST00000403750.5	c.178-132G>A		intron_variant		2		ENSP00000384403	A2

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9048 AN: 152126 Hom.: 390 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0320

Gnomad OTH AF: 0.0555

GnomAD4 exome AF: 0.0406 AC: 21927 AN: 539762 Hom.: 765 AF XY: 0.0417 AC XY: 11898 AN XY: 285188

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0234

Gnomad4 ASJ exome AF: 0.0183

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.0651

Gnomad4 FIN exome AF: 0.0158

Gnomad4 NFE exome AF: 0.0309

Gnomad4 OTH exome AF: 0.0487

GnomAD4 genome AF: 0.0595 AC: 9054 AN: 152244 Hom.: 391 Cov.: 33 AF XY: 0.0590 AC XY: 4395 AN XY: 74438

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0431

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.0687

Gnomad4 FIN AF: 0.0132

Gnomad4 NFE AF: 0.0320

Gnomad4 OTH AF: 0.0545

Alfa AF: 0.0384 Hom.: 72

Bravo AF: 0.0649

Asia WGS AF: 0.0920 AC: 319 AN: 3478

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

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11749124; hg19: chr5-149206104;