chr5-149820839-A-G

Position:

• chr5-149820839-A-G

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.252+233A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0706 in 152,186 control chromosomes in the GnomAD database, including 501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.071 (501 hom., cov: 32)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.319

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 5-149820839-A-G is Benign according to our data. Variant chr5-149820839-A-G is described in ClinVar as [Benign]. Clinvar id is 1227974.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.252+233A>G		intron_variant		ENST00000309241.10	NP_573570.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.252+233A>G		intron_variant		1	NM_133263.4	ENSP00000312649	P2
PPARGC1B	ENST00000360453.8	c.252+233A>G		intron_variant		1		ENSP00000353638	A2
PPARGC1B	ENST00000394320.7	c.252+233A>G		intron_variant		1		ENSP00000377855	A2
PPARGC1B	ENST00000403750.5	c.177+233A>G		intron_variant		2		ENSP00000384403	A2

Frequencies

GnomAD3 genomes AF: 0.0707 AC: 10748 AN: 152068 Hom.: 501 Cov.: 32

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0500

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0508

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0809

Gnomad OTH AF: 0.0904

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

GnomAD4 genome AF: 0.0706 AC: 10747 AN: 152186 Hom.: 501 Cov.: 32 AF XY: 0.0718 AC XY: 5343 AN XY: 74420

Gnomad4 AFR AF: 0.0258

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0501

Gnomad4 SAS AF: 0.0582

Gnomad4 FIN AF: 0.0508

Gnomad4 NFE AF: 0.0809

Gnomad4 OTH AF: 0.0900

Alfa AF: 0.0863 Hom.: 604

Bravo AF: 0.0771

Asia WGS AF: 0.0430 AC: 150 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 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs17462080; hg19: chr5-149200402;