rs11749124

Variant names:

• chr5-149826541-G-A
• rs11749124
• NM_133263.4:c.253-132G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_133263.4(PPARGC1B):​c.253-132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 692,006 control chromosomes in the GnomAD database, including 1,156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.059 (391 hom., cov: 33)
  • Exomes 𝑓: 0.041 (765 hom.)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.379
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-149826541-G-A is Benign according to our data. Variant chr5-149826541-G-A is described in ClinVar as Benign. ClinVar VariationId is 1237166.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133263.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1B	NM_133263.4	MANE Select	c.253-132G>A		intron	N/A	NP_573570.3
	PPARGC1B	NM_001172698.2		c.253-132G>A		intron	N/A	NP_001166169.1	Q86YN6-5
	PPARGC1B	NM_001172699.2		c.178-132G>A		intron	N/A	NP_001166170.1	Q86YN6-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1B	ENST00000309241.10	TSL:1 MANE Select	c.253-132G>A		intron	N/A	ENSP00000312649.5	Q86YN6-1
	PPARGC1B	ENST00000394320.7	TSL:1	c.253-132G>A		intron	N/A	ENSP00000377855.3	Q86YN6-3
	PPARGC1B	ENST00000360453.8	TSL:1	c.253-132G>A		intron	N/A	ENSP00000353638.4	Q86YN6-5

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9048 AN: 152126 Hom.: 390 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0320

Gnomad OTH AF: 0.0555

GnomAD4 exome AF: 0.0406 AC: 21927 AN: 539762 Hom.: 765 AF XY: 0.0417 AC XY: 11898 AN XY: 285188

African (AFR) AF: 0.113 AC: 1694 AN: 14940

American (AMR) AF: 0.0234 AC: 675 AN: 28866

Ashkenazi Jewish (ASJ) AF: 0.0183 AC: 279 AN: 15220

East Asian (EAS) AF: 0.115 AC: 3772 AN: 32822

South Asian (SAS) AF: 0.0651 AC: 3464 AN: 53222

European-Finnish (FIN) AF: 0.0158 AC: 729 AN: 46204

Middle Eastern (MID) AF: 0.0421 AC: 120 AN: 2848

European-Non Finnish (NFE) AF: 0.0309 AC: 9775 AN: 316514

Other (OTH) AF: 0.0487 AC: 1419 AN: 29126

GnomAD4 genome AF: 0.0595 AC: 9054 AN: 152244 Hom.: 391 Cov.: 33 AF XY: 0.0590 AC XY: 4395 AN XY: 74438

African (AFR) AF: 0.117 AC: 4874 AN: 41538

American (AMR) AF: 0.0431 AC: 659 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3468

East Asian (EAS) AF: 0.128 AC: 659 AN: 5168

South Asian (SAS) AF: 0.0687 AC: 331 AN: 4820

European-Finnish (FIN) AF: 0.0132 AC: 140 AN: 10614

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0320 AC: 2178 AN: 68012

Other (OTH) AF: 0.0545 AC: 115 AN: 2112

Alfa AF: 0.0429 Hom.: 144

Bravo AF: 0.0649

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.56
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11749124; hg19: chr5-149206104;