rs32589

Variant names:

• chr5-149820326-G-A
• rs32589
• NM_133263.4:c.79-107G>A

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.79-107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,053,444 control chromosomes in the GnomAD database, including 12,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2565 hom., cov: 32)
  • Exomes 𝑓: 0.14 (9498 hom.)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01
• Publications: 8 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=-0.9).
• BP6: Variant 5-149820326-G-A is Benign according to our data. Variant chr5-149820326-G-A is described in ClinVar as Benign. ClinVar VariationId is 1245490.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.79-107G>A		intron_variant	Intron 1 of 11	ENST00000309241.10	NP_573570.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.79-107G>A		intron_variant	Intron 1 of 11	1	NM_133263.4	ENSP00000312649.5
PPARGC1B	ENST00000394320.7	c.79-107G>A		intron_variant	Intron 1 of 10	1		ENSP00000377855.3
PPARGC1B	ENST00000360453.8	c.79-107G>A		intron_variant	Intron 1 of 10	1		ENSP00000353638.4
PPARGC1B	ENST00000403750.5	c.4-107G>A		intron_variant	Intron 1 of 10	2		ENSP00000384403.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25996 AN: 151934 Hom.: 2559 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0766

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.136 AC: 122493 AN: 901390 Hom.: 9498 AF XY: 0.140 AC XY: 63875 AN XY: 457634

African (AFR) AF: 0.249 AC: 5361 AN: 21566

American (AMR) AF: 0.0776 AC: 2384 AN: 30722

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 2552 AN: 17532

East Asian (EAS) AF: 0.0745 AC: 2720 AN: 36490

South Asian (SAS) AF: 0.218 AC: 13348 AN: 61134

European-Finnish (FIN) AF: 0.233 AC: 8869 AN: 38060

Middle Eastern (MID) AF: 0.162 AC: 654 AN: 4040

European-Non Finnish (NFE) AF: 0.124 AC: 80892 AN: 650816

Other (OTH) AF: 0.139 AC: 5713 AN: 41030

GnomAD4 genome AF: 0.171 AC: 26011 AN: 152054 Hom.: 2565 Cov.: 32 AF XY: 0.176 AC XY: 13052 AN XY: 74328

African (AFR) AF: 0.246 AC: 10198 AN: 41462

American (AMR) AF: 0.105 AC: 1602 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3468

East Asian (EAS) AF: 0.0768 AC: 397 AN: 5170

South Asian (SAS) AF: 0.212 AC: 1022 AN: 4814

European-Finnish (FIN) AF: 0.254 AC: 2681 AN: 10546

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9110 AN: 67986

Other (OTH) AF: 0.150 AC: 317 AN: 2114

Alfa AF: 0.139 Hom.: 3065

Bravo AF: 0.158

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.42
DANN	Benign	0.60
PhyloP100		-1.0
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: rs32589; hg19: chr5-149199889;