chr5-149826377-G-A

Position:

• chr5-149826377-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.253-296G>A		intron_variant		ENST00000309241.10	NP_573570.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.253-296G>A		intron_variant		1	NM_133263.4	ENSP00000312649	P2
PPARGC1B	ENST00000360453.8	c.253-296G>A		intron_variant		1		ENSP00000353638	A2
PPARGC1B	ENST00000394320.7	c.253-296G>A		intron_variant		1		ENSP00000377855	A2
PPARGC1B	ENST00000403750.5	c.178-296G>A		intron_variant		2		ENSP00000384403	A2

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

Gnomad4 AFR AF: 0.0583

Gnomad4 AMR AF: 0.0352

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.0690

Gnomad4 FIN AF: 0.0133

Gnomad4 NFE AF: 0.0318

Gnomad4 OTH AF: 0.0422

Alfa AF: 0.0309 Hom.: 102

Bravo AF: 0.0451

Asia WGS AF: 0.102 AC: 355 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.50
DANN	Benign	0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs2003604; hg19: chr5-149205940;