rs32589

Positions:

• chr5-149820326-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.79-107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,053,444 control chromosomes in the GnomAD database, including 12,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2565 hom., cov: 32)
  • Exomes 𝑓: 0.14 (9498 hom.)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

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=-0.9).
• BP6: Variant 5-149820326-G-A is Benign according to our data. Variant chr5-149820326-G-A is described in ClinVar as [Benign]. Clinvar id is 1245490.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.79-107G>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.79-107G>A		intron_variant		1	NM_133263.4	ENSP00000312649	P2
PPARGC1B	ENST00000360453.8	c.79-107G>A		intron_variant		1		ENSP00000353638	A2
PPARGC1B	ENST00000394320.7	c.79-107G>A		intron_variant		1		ENSP00000377855	A2
PPARGC1B	ENST00000403750.5	c.4-107G>A		intron_variant		2		ENSP00000384403	A2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25996 AN: 151934 Hom.: 2559 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0766

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.136 AC: 122493 AN: 901390 Hom.: 9498 AF XY: 0.140 AC XY: 63875 AN XY: 457634

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.0776

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.0745

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.171 AC: 26011 AN: 152054 Hom.: 2565 Cov.: 32 AF XY: 0.176 AC XY: 13052 AN XY: 74328

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.0768

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.150

Alfa AF: 0.137 Hom.: 2174

Bravo AF: 0.158

Asia WGS AF: 0.137 AC: 477 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	-0.90
CADD	Benign	0.42
DANN	Benign	0.60

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: rs32589; hg19: chr5-149199889;