NM_133263.4:c.78+41465A>G

Variant names:

• chr5-149771885-A-G
• rs4705375
• NM_133263.4:c.78+41465A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133263.4(PPARGC1B):​c.78+41465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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.78+41465A>G		intron	N/A	NP_573570.3
	PPARGC1B	NM_001172698.2		c.78+41465A>G		intron	N/A	NP_001166169.1	Q86YN6-5
	PPARGC1B	NM_001172699.2		c.-252A>G		upstream_gene	N/A	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.78+41465A>G		intron	N/A	ENSP00000312649.5	Q86YN6-1
	PPARGC1B	ENST00000394320.7	TSL:1	c.78+41465A>G		intron	N/A	ENSP00000377855.3	Q86YN6-3
	PPARGC1B	ENST00000360453.8	TSL:1	c.78+41465A>G		intron	N/A	ENSP00000353638.4	Q86YN6-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 536644 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 269534

African (AFR) AF: 0.00 AC: 0 AN: 12078

American (AMR) AF: 0.00 AC: 0 AN: 10596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11472

East Asian (EAS) AF: 0.00 AC: 0 AN: 21306

South Asian (SAS) AF: 0.00 AC: 0 AN: 31988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1982

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 397830

Other (OTH) AF: 0.00 AC: 0 AN: 26006

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.83
DANN	Benign	0.81
PhyloP100		-0.25
PromoterAI		-0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.98

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: rs4705375; hg19: chr5-149151448;