chr5-149816671-G-C

Variant names:

• chr5-149816671-G-C
• rs251464
• NM_133263.4:c.79-3762G>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.79-3762G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,080 control chromosomes in the GnomAD database, including 10,499 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 0.35 (10499 hom., cov: 32)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 17 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 = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.79-3762G>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.79-3762G>C		intron_variant	Intron 1 of 11	1	NM_133263.4	ENSP00000312649.5

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53507 AN: 151960 Hom.: 10472 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.352 AC: 53594 AN: 152080 Hom.: 10499 Cov.: 32 AF XY: 0.358 AC XY: 26604 AN XY: 74336

African (AFR) AF: 0.506 AC: 20982 AN: 41460

American (AMR) AF: 0.418 AC: 6385 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3468

East Asian (EAS) AF: 0.215 AC: 1115 AN: 5176

South Asian (SAS) AF: 0.310 AC: 1493 AN: 4818

European-Finnish (FIN) AF: 0.367 AC: 3871 AN: 10560

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17560 AN: 67998

Other (OTH) AF: 0.334 AC: 704 AN: 2110

Alfa AF: 0.192 Hom.: 390

Bravo AF: 0.365

Asia WGS AF: 0.255 AC: 885 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	1.8
DANN	Benign	0.43
PhyloP100		-0.22
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: rs251464; hg19: chr5-149196234;