chr5-149771756-C-T

Position:

• chr5-149771756-C-T

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.78+41336C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,226 control chromosomes in the GnomAD database, including 1,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1316 hom., cov: 33)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.559

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=-0.95).
• BP6: Variant 5-149771756-C-T is Benign according to our data. Variant chr5-149771756-C-T is described in ClinVar as [Benign]. Clinvar id is 1257595.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.78+41336C>T		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+41336C>T		intron_variant		1	NM_133263.4	ENSP00000312649	P2
PPARGC1B	ENST00000360453.8	c.78+41336C>T		intron_variant		1		ENSP00000353638	A2
PPARGC1B	ENST00000394320.7	c.78+41336C>T		intron_variant		1		ENSP00000377855	A2
PPARGC1B	ENST00000461780.1	n.432+10144C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17409 AN: 152108 Hom.: 1313 Cov.: 33

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0834

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.114 AC: 17421 AN: 152226 Hom.: 1316 Cov.: 33 AF XY: 0.116 AC XY: 8650 AN XY: 74424

Gnomad4 AFR AF: 0.0314

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0832

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.138

Alfa AF: 0.132 Hom.: 665

Bravo AF: 0.123

Asia WGS AF: 0.111 AC: 390 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	-0.95
CADD	Benign	4.4
DANN	Benign	0.46

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: rs4705374; hg19: chr5-149151319;