rs10491360

Variant names:

• chr5-149818252-T-C
• rs10491360
• NM_133263.4:c.79-2181T>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.79-2181T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,272 control chromosomes in the GnomAD database, including 1,361 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 (1361 hom., cov: 33)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.79-2181T>C		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.79-2181T>C		intron_variant	Intron 1 of 11	1	NM_133263.4	ENSP00000312649.5
PPARGC1B	ENST00000394320.7	c.79-2181T>C		intron_variant	Intron 1 of 10	1		ENSP00000377855.3
PPARGC1B	ENST00000360453.8	c.79-2181T>C		intron_variant	Intron 1 of 10	1		ENSP00000353638.4
PPARGC1B	ENST00000403750.5	c.4-2181T>C		intron_variant	Intron 1 of 10	2		ENSP00000384403.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16071 AN: 152154 Hom.: 1347 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.0878

Gnomad SAS AF: 0.0374

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0433

Gnomad OTH AF: 0.0884

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

GnomAD4 genome AF: 0.106 AC: 16136 AN: 152272 Hom.: 1361 Cov.: 33 AF XY: 0.106 AC XY: 7863 AN XY: 74460

African (AFR) AF: 0.218 AC: 9055 AN: 41528

American (AMR) AF: 0.165 AC: 2519 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3472

East Asian (EAS) AF: 0.0875 AC: 453 AN: 5180

South Asian (SAS) AF: 0.0377 AC: 182 AN: 4834

European-Finnish (FIN) AF: 0.0625 AC: 663 AN: 10612

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0432 AC: 2941 AN: 68022

Other (OTH) AF: 0.0908 AC: 192 AN: 2114

Alfa AF: 0.0737 Hom.: 173

Bravo AF: 0.124

Asia WGS AF: 0.0690 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.84
PhyloP100		-0.41
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: rs10491360; hg19: chr5-149197815;