rs10875552

Variant names:

• chr5-149809926-G-A
• rs10875552
• NM_133263.4:c.79-10507G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.79-10507G>A		intron_variant	Intron 1 of 11	ENST00000309241.10	NP_573570.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.79-10507G>A		intron_variant	Intron 1 of 11	1	NM_133263.4	ENSP00000312649.5

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

African (AFR) AF: 0.796 AC: 32884 AN: 41320

American (AMR) AF: 0.736 AC: 11230 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2118 AN: 3464

East Asian (EAS) AF: 0.898 AC: 4602 AN: 5124

South Asian (SAS) AF: 0.607 AC: 2906 AN: 4788

European-Finnish (FIN) AF: 0.635 AC: 6672 AN: 10512

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43247 AN: 67904

Other (OTH) AF: 0.682 AC: 1430 AN: 2096

Alfa AF: 0.660 Hom.: 56091

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
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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