NM_133263.4:c.78+32333T>C

Variant names:

• chr5-149762753-T-C
• rs2340621
• NM_133263.4:c.78+32333T>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.78+32333T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,040 control chromosomes in the GnomAD database, including 40,732 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 0.73 (40732 hom., cov: 31)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.78+32333T>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.78+32333T>C		intron_variant	Intron 1 of 11	1	NM_133263.4	ENSP00000312649.5
PPARGC1B	ENST00000394320.7	c.78+32333T>C		intron_variant	Intron 1 of 10	1		ENSP00000377855.3
PPARGC1B	ENST00000360453.8	c.78+32333T>C		intron_variant	Intron 1 of 10	1		ENSP00000353638.4
PPARGC1B	ENST00000461780.1	n.432+1141T>C		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110907 AN: 151922 Hom.: 40690 Cov.: 31

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.730 AC: 111007 AN: 152040 Hom.: 40732 Cov.: 31 AF XY: 0.728 AC XY: 54091 AN XY: 74298

African (AFR) AF: 0.821 AC: 34042 AN: 41488

American (AMR) AF: 0.754 AC: 11529 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2402 AN: 3472

East Asian (EAS) AF: 0.693 AC: 3571 AN: 5152

South Asian (SAS) AF: 0.754 AC: 3632 AN: 4816

European-Finnish (FIN) AF: 0.667 AC: 7037 AN: 10552

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46504 AN: 67962

Other (OTH) AF: 0.715 AC: 1510 AN: 2112

Alfa AF: 0.703 Hom.: 99593

Bravo AF: 0.741

Asia WGS AF: 0.760 AC: 2644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.74
DANN	Benign	0.40
PhyloP100		-1.2
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: rs2340621; hg19: chr5-149142316; COSMIC: COSV58527648;