5-149833893-A-G

Variant names:

• chr5-149833893-A-G
• rs32576
• NM_133263.4:c.1705+115A>G

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.1705+115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,397,596 control chromosomes in the GnomAD database, including 41,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7639 hom., cov: 33)
  • Exomes 𝑓: 0.23 (34337 hom.)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.404
• Publications: 7 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 5-149833893-A-G is Benign according to our data. Variant chr5-149833893-A-G is described in ClinVar as Benign. ClinVar VariationId is 1273814.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1B	NM_133263.4	MANE Select	c.1705+115A>G		intron	N/A	NP_573570.3
	PPARGC1B	NM_001172698.2		c.1588+115A>G		intron	N/A	NP_001166169.1
	PPARGC1B	NM_001172699.2		c.1513+115A>G		intron	N/A	NP_001166170.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1B	ENST00000309241.10	TSL:1 MANE Select	c.1705+115A>G		intron	N/A	ENSP00000312649.5
	PPARGC1B	ENST00000394320.7	TSL:1	c.1705+115A>G		intron	N/A	ENSP00000377855.3
	PPARGC1B	ENST00000360453.8	TSL:1	c.1588+115A>G		intron	N/A	ENSP00000353638.4

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45786 AN: 151986 Hom.: 7608 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.228 AC: 283640 AN: 1245492 Hom.: 34337 AF XY: 0.230 AC XY: 137743 AN XY: 599790

African (AFR) AF: 0.453 AC: 12509 AN: 27632

American (AMR) AF: 0.330 AC: 5842 AN: 17710

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 4003 AN: 18506

East Asian (EAS) AF: 0.266 AC: 8997 AN: 33820

South Asian (SAS) AF: 0.331 AC: 17491 AN: 52848

European-Finnish (FIN) AF: 0.320 AC: 9461 AN: 29520

Middle Eastern (MID) AF: 0.259 AC: 942 AN: 3634

European-Non Finnish (NFE) AF: 0.209 AC: 211445 AN: 1009778

Other (OTH) AF: 0.249 AC: 12950 AN: 52044

GnomAD4 genome AF: 0.302 AC: 45874 AN: 152104 Hom.: 7639 Cov.: 33 AF XY: 0.308 AC XY: 22880 AN XY: 74352

African (AFR) AF: 0.436 AC: 18103 AN: 41490

American (AMR) AF: 0.302 AC: 4619 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3470

East Asian (EAS) AF: 0.288 AC: 1490 AN: 5170

South Asian (SAS) AF: 0.328 AC: 1582 AN: 4824

European-Finnish (FIN) AF: 0.339 AC: 3586 AN: 10568

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14940 AN: 67982

Other (OTH) AF: 0.276 AC: 582 AN: 2110

Alfa AF: 0.263 Hom.: 8771

Bravo AF: 0.307

Asia WGS AF: 0.318 AC: 1108 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.64
PhyloP100		-0.40
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: rs32576; hg19: chr5-149213456;