rs109075

chr5-149815360-T-C

Variant summary

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

The NM_133263.4(PPARGC1B):c.79-5073T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,590 control chromosomes in the GnomAD database, including 14,883 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 0.42 (14883 hom., cov: 30)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1B	NM_133263.4	c.79-5073T>C		intron_variant		ENST00000309241.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.79-5073T>C		intron_variant		1	NM_133263.4	P2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63151 AN: 151472 Hom.: 14842 Cov.: 30

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.417 AC: 63255 AN: 151590 Hom.: 14883 Cov.: 30 AF XY: 0.422 AC XY: 31263 AN XY: 74008

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.390

Alfa AF: 0.315 Hom.: 12905

Bravo AF: 0.434

Asia WGS AF: 0.364 AC: 1264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.62
Dann	Benign	0.53

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: rs109075; hg19: chr5-149194923;