rs6895698

Positions:

• chr5-149760699-A-G
• chr5-149760699-A-T

Variant summary

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

The NM_133263.4(PPARGC1B):​c.78+30279A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,168 control chromosomes in the GnomAD database, including 49,968 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 0.81 (49968 hom., cov: 32)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.78+30279A>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.78+30279A>G		intron_variant		1	NM_133263.4	ENSP00000312649	P2
PPARGC1B	ENST00000360453.8	c.78+30279A>G		intron_variant		1		ENSP00000353638	A2
PPARGC1B	ENST00000394320.7	c.78+30279A>G		intron_variant		1		ENSP00000377855	A2
PPARGC1B	ENST00000461780.1	n.252-733A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122995 AN: 152050 Hom.: 49914 Cov.: 32

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.809 AC: 123113 AN: 152168 Hom.: 49968 Cov.: 32 AF XY: 0.811 AC XY: 60356 AN XY: 74392

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.885

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.789

Alfa AF: 0.788 Hom.: 9774

Bravo AF: 0.809

Asia WGS AF: 0.868 AC: 3020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.72

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: rs6895698; hg19: chr5-149140262; COSMIC: COSV58527629;