rs4705372

Positions:

• chr5-149759262-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133263.4(PPARGC1B):​c.78+28842G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,222 control chromosomes in the GnomAD database, including 1,318 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1318 hom., cov: 32)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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]

PPARGC1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.78+28842G>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.78+28842G>A		intron_variant		1	NM_133263.4	ENSP00000312649.5
PPARGC1B	ENST00000394320.7	c.78+28842G>A		intron_variant		1		ENSP00000377855.3
PPARGC1B	ENST00000360453.8	c.78+28842G>A		intron_variant		1		ENSP00000353638.4
PPARGC1B	ENST00000461780.1	n.252-2170G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17389 AN: 152104 Hom.: 1317 Cov.: 32

Gnomad AFR AF: 0.0280

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0970

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.134

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17399 AN: 152222 Hom.: 1318 Cov.: 32 AF XY: 0.117 AC XY: 8685 AN XY: 74400

Gnomad4 AFR AF: 0.0279

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0964

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.137

Alfa AF: 0.131 Hom.: 285

Bravo AF: 0.123

Asia WGS AF: 0.115 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.65
DANN	Benign	0.58

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: rs4705372; hg19: chr5-149138825;