chr5-149832908-G-A

Variant names:

• chr5-149832908-G-A
• rs17572019
• NM_133263.4:c.835G>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.835G>A​(p.Val279Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 1,613,074 control chromosomes in the GnomAD database, including 5,688 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (476 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5212 hom.)
• Consequence: PPARGC1B NM_133263.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.967
• Publications: 25 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 (MetaRNN=0.0014909208).
• BP6: Variant 5-149832908-G-A is Benign according to our data. Variant chr5-149832908-G-A is described in ClinVar as Benign. ClinVar VariationId is 1288207.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 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.835G>A	p.Val279Ile	missense	Exon 5 of 12	NP_573570.3
	PPARGC1B	NM_001172698.2		c.718G>A	p.Val240Ile	missense	Exon 4 of 11	NP_001166169.1	Q86YN6-5
	PPARGC1B	NM_001172699.2		c.643G>A	p.Val215Ile	missense	Exon 4 of 11	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.835G>A	p.Val279Ile	missense	Exon 5 of 12	ENSP00000312649.5	Q86YN6-1
	PPARGC1B	ENST00000394320.7	TSL:1	c.835G>A	p.Val279Ile	missense	Exon 5 of 11	ENSP00000377855.3	Q86YN6-3
	PPARGC1B	ENST00000360453.8	TSL:1	c.718G>A	p.Val240Ile	missense	Exon 4 of 11	ENSP00000353638.4	Q86YN6-5

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10695 AN: 152114 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.0460

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.0886

GnomAD2 exomes AF: 0.0854 AC: 21193 AN: 248096 AF XY: 0.0841

Gnomad AFR exome AF: 0.0280

Gnomad AMR exome AF: 0.150

Gnomad ASJ exome AF: 0.149

Gnomad EAS exome AF: 0.0645

Gnomad FIN exome AF: 0.0490

Gnomad NFE exome AF: 0.0834

Gnomad OTH exome AF: 0.0845

GnomAD4 exome AF: 0.0816 AC: 119206 AN: 1460842 Hom.: 5212 Cov.: 32 AF XY: 0.0812 AC XY: 59010 AN XY: 726694

African (AFR) AF: 0.0260 AC: 870 AN: 33480

American (AMR) AF: 0.148 AC: 6636 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 3861 AN: 26128

East Asian (EAS) AF: 0.0577 AC: 2291 AN: 39700

South Asian (SAS) AF: 0.0655 AC: 5648 AN: 86252

European-Finnish (FIN) AF: 0.0500 AC: 2622 AN: 52460

Middle Eastern (MID) AF: 0.100 AC: 578 AN: 5768

European-Non Finnish (NFE) AF: 0.0824 AC: 91620 AN: 1111960

Other (OTH) AF: 0.0841 AC: 5080 AN: 60382

GnomAD4 genome AF: 0.0702 AC: 10694 AN: 152232 Hom.: 476 Cov.: 32 AF XY: 0.0712 AC XY: 5303 AN XY: 74432

African (AFR) AF: 0.0285 AC: 1185 AN: 41554

American (AMR) AF: 0.145 AC: 2212 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3472

East Asian (EAS) AF: 0.0596 AC: 308 AN: 5170

South Asian (SAS) AF: 0.0612 AC: 295 AN: 4824

European-Finnish (FIN) AF: 0.0460 AC: 488 AN: 10612

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0798 AC: 5423 AN: 67998

Other (OTH) AF: 0.0882 AC: 186 AN: 2110

Alfa AF: 0.0809 Hom.: 1483

Bravo AF: 0.0763

TwinsUK AF: 0.0771 AC: 286

ALSPAC AF: 0.0823 AC: 317

ESP6500AA AF: 0.0284 AC: 125

ESP6500EA AF: 0.0834 AC: 717

ExAC AF: 0.0802 AC: 9732

Asia WGS AF: 0.0480 AC: 167 AN: 3478

EpiCase AF: 0.0876

EpiControl AF: 0.0862

ClinVar

ClinVar submissions

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
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.93
DANN	Benign	0.91
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.97
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.043
Sift	Benign	0.047	D
Sift4G	Benign	0.52	T
Polyphen		0.010	B
Vest4		0.034
MPC		0.14
ClinPred		0.010	T
GERP RS		-1.7
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.064
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: rs17572019; hg19: chr5-149212471; COSMIC: COSV107361531; COSMIC: COSV107361531;