rs10875552

Positions:

• chr5-149809926-G-A
• chr5-149809926-G-C

Variant summary

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

The NM_133263.4(PPARGC1B):​c.79-10507G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 151,666 control chromosomes in the GnomAD database, including 37,527 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 0.70 (37527 hom., cov: 28)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1B	NM_133263.4	c.79-10507G>A		intron_variant		ENST00000309241.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.79-10507G>A		intron_variant		1	NM_133263.4	P2

Frequencies

GnomAD3 genomes AF: 0.699 AC: 105889 AN: 151548 Hom.: 37487 Cov.: 28

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.699 AC: 105983 AN: 151666 Hom.: 37527 Cov.: 28 AF XY: 0.700 AC XY: 51891 AN XY: 74102

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.682

Alfa AF: 0.649 Hom.: 32755

Bravo AF: 0.718

Asia WGS AF: 0.718 AC: 2497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.72
DANN	Benign	0.76

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: rs10875552; hg19: chr5-149189489; COSMIC: COSV58527769;