rs1076064

Variant names:

• chr5-149732603-A-G
• rs1076064
• NM_133263.4:c.78+2183A>G

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+2183A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,116 control chromosomes in the GnomAD database, including 17,644 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 0.47 (17644 hom., cov: 33)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 15 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]

MIR378A (HGNC:31871): (microRNA 378a) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.78+2183A>G		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+2183A>G		intron_variant	Intron 1 of 11	1	NM_133263.4	ENSP00000312649.5

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71107 AN: 151998 Hom.: 17610 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.468 AC: 71199 AN: 152116 Hom.: 17644 Cov.: 33 AF XY: 0.469 AC XY: 34878 AN XY: 74366

African (AFR) AF: 0.640 AC: 26547 AN: 41504

American (AMR) AF: 0.488 AC: 7462 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2612 AN: 5162

South Asian (SAS) AF: 0.464 AC: 2237 AN: 4818

European-Finnish (FIN) AF: 0.371 AC: 3917 AN: 10572

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25724 AN: 67980

Other (OTH) AF: 0.469 AC: 992 AN: 2116

Alfa AF: 0.428 Hom.: 1918

Bravo AF: 0.487

Asia WGS AF: 0.507 AC: 1763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Benign	0.44
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1076064; hg19: chr5-149112166; COSMIC: COSV58527466; COSMIC: COSV58527466;