NM_133263.4:c.1164G>A

Variant names:

• chr5-149833237-G-A
• rs32577
• NM_133263.4:c.1164G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_133263.4(PPARGC1B):​c.1164G>A​(p.Pro388Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,613,216 control chromosomes in the GnomAD database, including 18,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2232 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15782 hom.)
• Consequence: PPARGC1B NM_133263.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.54
• Publications: 13 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.02).
• BP6: Variant 5-149833237-G-A is Benign according to our data. Variant chr5-149833237-G-A is described in ClinVar as Benign. ClinVar VariationId is 1276406.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1B	NM_133263.4	MANE Select	c.1164G>A	p.Pro388Pro	synonymous	Exon 5 of 12	NP_573570.3
	PPARGC1B	NM_001172698.2		c.1047G>A	p.Pro349Pro	synonymous	Exon 4 of 11	NP_001166169.1
	PPARGC1B	NM_001172699.2		c.972G>A	p.Pro324Pro	synonymous	Exon 4 of 11	NP_001166170.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1B	ENST00000309241.10	TSL:1 MANE Select	c.1164G>A	p.Pro388Pro	synonymous	Exon 5 of 12	ENSP00000312649.5
	PPARGC1B	ENST00000394320.7	TSL:1	c.1164G>A	p.Pro388Pro	synonymous	Exon 5 of 11	ENSP00000377855.3
	PPARGC1B	ENST00000360453.8	TSL:1	c.1047G>A	p.Pro349Pro	synonymous	Exon 4 of 11	ENSP00000353638.4

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24861 AN: 152096 Hom.: 2227 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0983

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.140

GnomAD2 exomes AF: 0.146 AC: 36567 AN: 249672 AF XY: 0.153

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.0708

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.00555

Gnomad FIN exome AF: 0.244

Gnomad NFE exome AF: 0.141

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.139 AC: 203136 AN: 1461004 Hom.: 15782 Cov.: 35 AF XY: 0.143 AC XY: 103731 AN XY: 726798

African (AFR) AF: 0.233 AC: 7789 AN: 33480

American (AMR) AF: 0.0744 AC: 3326 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 4252 AN: 26136

East Asian (EAS) AF: 0.0261 AC: 1038 AN: 39700

South Asian (SAS) AF: 0.225 AC: 19408 AN: 86256

European-Finnish (FIN) AF: 0.242 AC: 12731 AN: 52564

Middle Eastern (MID) AF: 0.176 AC: 1013 AN: 5768

European-Non Finnish (NFE) AF: 0.131 AC: 145249 AN: 1111986

Other (OTH) AF: 0.138 AC: 8330 AN: 60390

GnomAD4 genome AF: 0.164 AC: 24888 AN: 152212 Hom.: 2232 Cov.: 33 AF XY: 0.169 AC XY: 12571 AN XY: 74434

African (AFR) AF: 0.216 AC: 8988 AN: 41518

American (AMR) AF: 0.0981 AC: 1502 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 570 AN: 3470

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5176

South Asian (SAS) AF: 0.216 AC: 1040 AN: 4818

European-Finnish (FIN) AF: 0.262 AC: 2782 AN: 10602

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.139 AC: 9467 AN: 68002

Other (OTH) AF: 0.139 AC: 295 AN: 2116

Alfa AF: 0.145 Hom.: 1373

Bravo AF: 0.150

Asia WGS AF: 0.121 AC: 422 AN: 3478

EpiCase AF: 0.135

EpiControl AF: 0.134

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	-0.95
CADD	Benign	0.089
DANN	Benign	0.57
PhyloP100		-3.5
PromoterAI		-0.021	Neutral
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: rs32577; hg19: chr5-149212800; COSMIC: COSV58529297;