NM_133263.4:c.78+41336C>T

Variant names:

• chr5-149771756-C-T
• rs4705374
• NM_133263.4:c.78+41336C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_133263.4(PPARGC1B):​c.78+41336C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,226 control chromosomes in the GnomAD database, including 1,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1316 hom., cov: 33)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.559
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-149771756-C-T is Benign according to our data. Variant chr5-149771756-C-T is described in ClinVar as Benign. ClinVar VariationId is 1257595.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1B	NM_133263.4	MANE Select	c.78+41336C>T		intron	N/A	NP_573570.3
	PPARGC1B	NM_001172698.2		c.78+41336C>T		intron	N/A	NP_001166169.1	Q86YN6-5
	PPARGC1B	NM_001172699.2		c.-381C>T		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+41336C>T		intron	N/A	ENSP00000312649.5	Q86YN6-1
	PPARGC1B	ENST00000394320.7	TSL:1	c.78+41336C>T		intron	N/A	ENSP00000377855.3	Q86YN6-3
	PPARGC1B	ENST00000360453.8	TSL:1	c.78+41336C>T		intron	N/A	ENSP00000353638.4	Q86YN6-5

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17409 AN: 152108 Hom.: 1313 Cov.: 33

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0834

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.114 AC: 17421 AN: 152226 Hom.: 1316 Cov.: 33 AF XY: 0.116 AC XY: 8650 AN XY: 74424

African (AFR) AF: 0.0314 AC: 1306 AN: 41538

American (AMR) AF: 0.236 AC: 3601 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 543 AN: 3468

East Asian (EAS) AF: 0.0832 AC: 431 AN: 5182

South Asian (SAS) AF: 0.165 AC: 795 AN: 4822

European-Finnish (FIN) AF: 0.118 AC: 1252 AN: 10594

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9034 AN: 68012

Other (OTH) AF: 0.138 AC: 292 AN: 2114

Alfa AF: 0.133 Hom.: 752

Bravo AF: 0.123

Asia WGS AF: 0.111 AC: 390 AN: 3478

ClinVar

ClinVar submissions

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	4.4
DANN	Benign	0.46
PhyloP100		-0.56
PromoterAI		-0.15	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: rs4705374; hg19: chr5-149151319;