rs2003604

Variant names:

• chr5-149826377-G-A
• rs2003604
• NM_133263.4:c.253-296G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-149826377-G-A
• chr5-149826377-G-C

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.253-296G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 152,182 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.043 (188 hom., cov: 33)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.427
• Publications: 4 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=-0.91).
• BP6: Variant 5-149826377-G-A is Benign according to our data. Variant chr5-149826377-G-A is described in ClinVar as Benign. ClinVar VariationId is 1263688.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 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.253-296G>A		intron	N/A	NP_573570.3
	PPARGC1B	NM_001172698.2		c.253-296G>A		intron	N/A	NP_001166169.1	Q86YN6-5
	PPARGC1B	NM_001172699.2		c.178-296G>A		intron	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.253-296G>A		intron	N/A	ENSP00000312649.5	Q86YN6-1
	PPARGC1B	ENST00000394320.7	TSL:1	c.253-296G>A		intron	N/A	ENSP00000377855.3	Q86YN6-3
	PPARGC1B	ENST00000360453.8	TSL:1	c.253-296G>A		intron	N/A	ENSP00000353638.4	Q86YN6-5

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6537 AN: 152064 Hom.: 187 Cov.: 33

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0318

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0430 AC: 6537 AN: 152182 Hom.: 188 Cov.: 33 AF XY: 0.0429 AC XY: 3194 AN XY: 74410

African (AFR) AF: 0.0583 AC: 2420 AN: 41508

American (AMR) AF: 0.0352 AC: 539 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3472

East Asian (EAS) AF: 0.145 AC: 752 AN: 5170

South Asian (SAS) AF: 0.0690 AC: 332 AN: 4814

European-Finnish (FIN) AF: 0.0133 AC: 141 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0318 AC: 2162 AN: 67992

Other (OTH) AF: 0.0422 AC: 89 AN: 2110

Alfa AF: 0.0323 Hom.: 154

Bravo AF: 0.0451

Asia WGS AF: 0.102 AC: 355 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	-0.91
CADD	Benign	0.50
DANN	Benign	0.28
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2003604; hg19: chr5-149205940;