rs32576

Positions:

• chr5-149833893-A-G

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.1705+115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,397,596 control chromosomes in the GnomAD database, including 41,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7639 hom., cov: 33)
  • Exomes 𝑓: 0.23 (34337 hom.)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.404

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=-0.95).
• BP6: Variant 5-149833893-A-G is Benign according to our data. Variant chr5-149833893-A-G is described in ClinVar as [Benign]. Clinvar id is 1273814.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.1705+115A>G		intron_variant		ENST00000309241.10	NP_573570.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.1705+115A>G		intron_variant		1	NM_133263.4	ENSP00000312649.5

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45786 AN: 151986 Hom.: 7608 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.228 AC: 283640 AN: 1245492 Hom.: 34337 AF XY: 0.230 AC XY: 137743 AN XY: 599790

Gnomad4 AFR exome AF: 0.453

Gnomad4 AMR exome AF: 0.330

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.302 AC: 45874 AN: 152104 Hom.: 7639 Cov.: 33 AF XY: 0.308 AC XY: 22880 AN XY: 74352

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.276

Alfa AF: 0.237 Hom.: 4348

Bravo AF: 0.307

Asia WGS AF: 0.318 AC: 1108 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.64

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: rs32576; hg19: chr5-149213456;