rs1078324

Variant names:

• chr5-149822705-C-A
• rs1078324
• NM_133263.4:c.252+2099C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-149822705-C-A
• chr5-149822705-C-T

Variant summary

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

The NM_133263.4(PPARGC1B):​c.252+2099C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 152,280 control chromosomes in the GnomAD database, including 532 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 0.075 (532 hom., cov: 32)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.823
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 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.252+2099C>A		intron	N/A	NP_573570.3
	PPARGC1B	NM_001172698.2		c.252+2099C>A		intron	N/A	NP_001166169.1
	PPARGC1B	NM_001172699.2		c.177+2099C>A		intron	N/A	NP_001166170.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1B	ENST00000309241.10	TSL:1 MANE Select	c.252+2099C>A		intron	N/A	ENSP00000312649.5
	PPARGC1B	ENST00000394320.7	TSL:1	c.252+2099C>A		intron	N/A	ENSP00000377855.3
	PPARGC1B	ENST00000360453.8	TSL:1	c.252+2099C>A		intron	N/A	ENSP00000353638.4

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11430 AN: 152162 Hom.: 528 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0514

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0583

Gnomad OTH AF: 0.0678

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

GnomAD4 genome AF: 0.0751 AC: 11439 AN: 152280 Hom.: 532 Cov.: 32 AF XY: 0.0743 AC XY: 5531 AN XY: 74460

African (AFR) AF: 0.117 AC: 4845 AN: 41540

American (AMR) AF: 0.0514 AC: 786 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3468

East Asian (EAS) AF: 0.160 AC: 831 AN: 5180

South Asian (SAS) AF: 0.0782 AC: 377 AN: 4820

European-Finnish (FIN) AF: 0.0308 AC: 327 AN: 10616

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0583 AC: 3965 AN: 68032

Other (OTH) AF: 0.0666 AC: 141 AN: 2116

Alfa AF: 0.0329 Hom.: 106

Bravo AF: 0.0785

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.52
PhyloP100		-0.82
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: rs1078324; hg19: chr5-149202268;