5-149816040-C-G

Variant names:

• chr5-149816040-C-G
• rs251466
• NM_133263.4:c.79-4393C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133263.4(PPARGC1B):​c.79-4393C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,980 control chromosomes in the GnomAD database, including 9,503 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 0.34 (9503 hom., cov: 32)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.79-4393C>G		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.79-4393C>G		intron_variant	Intron 1 of 11	1	NM_133263.4	ENSP00000312649.5

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51358 AN: 151862 Hom.: 9481 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.338 AC: 51432 AN: 151980 Hom.: 9503 Cov.: 32 AF XY: 0.344 AC XY: 25572 AN XY: 74306

African (AFR) AF: 0.458 AC: 18974 AN: 41436

American (AMR) AF: 0.411 AC: 6283 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1178 AN: 3464

East Asian (EAS) AF: 0.216 AC: 1116 AN: 5164

South Asian (SAS) AF: 0.310 AC: 1493 AN: 4820

European-Finnish (FIN) AF: 0.367 AC: 3871 AN: 10552

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17534 AN: 67956

Other (OTH) AF: 0.325 AC: 685 AN: 2106

Alfa AF: 0.315 Hom.: 999

Bravo AF: 0.349

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.49
PhyloP100		-0.044
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: rs251466; hg19: chr5-149195603;