chr5-149764400-G-A

Position:

• chr5-149764400-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133263.4(PPARGC1B):​c.78+33980G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 152,258 control chromosomes in the GnomAD database, including 631 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.079 (631 hom., cov: 32)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.78+33980G>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.78+33980G>A		intron_variant		1	NM_133263.4	ENSP00000312649	P2
PPARGC1B	ENST00000360453.8	c.78+33980G>A		intron_variant		1		ENSP00000353638	A2
PPARGC1B	ENST00000394320.7	c.78+33980G>A		intron_variant		1		ENSP00000377855	A2
PPARGC1B	ENST00000461780.1	n.432+2788G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 12053 AN: 152140 Hom.: 629 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0501

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.0824

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0330

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0566

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.0793 AC: 12072 AN: 152258 Hom.: 631 Cov.: 32 AF XY: 0.0780 AC XY: 5805 AN XY: 74450

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.0501

Gnomad4 ASJ AF: 0.0697

Gnomad4 EAS AF: 0.0822

Gnomad4 SAS AF: 0.0344

Gnomad4 FIN AF: 0.0330

Gnomad4 NFE AF: 0.0565

Gnomad4 OTH AF: 0.0758

Alfa AF: 0.0624 Hom.: 468

Bravo AF: 0.0836

Asia WGS AF: 0.0630 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.59

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: rs11746690; hg19: chr5-149143963;