5-149771885-A-T

Position:

• chr5-149771885-A-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+41465A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 686,486 control chromosomes in the GnomAD database, including 66,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (15107 hom., cov: 32)
  • Exomes 𝑓: 0.43 (51459 hom.)
• Consequence: PPARGC1B NM_133263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.252

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]

PPARGC1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-149771885-A-T is Benign according to our data. Variant chr5-149771885-A-T is described in ClinVar as [Benign]. Clinvar id is 1269943.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.78+41465A>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+41465A>T		intron_variant		1	NM_133263.4	ENSP00000312649.5
PPARGC1B	ENST00000394320.7	c.78+41465A>T		intron_variant		1		ENSP00000377855.3
PPARGC1B	ENST00000360453.8	c.78+41465A>T		intron_variant		1		ENSP00000353638.4
PPARGC1B	ENST00000461780.1	n.432+10273A>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67211 AN: 151892 Hom.: 15091 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.433 AC: 231577 AN: 534476 Hom.: 51459 AF XY: 0.430 AC XY: 115409 AN XY: 268482

Gnomad4 AFR exome AF: 0.474

Gnomad4 AMR exome AF: 0.354

Gnomad4 ASJ exome AF: 0.435

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.364

Gnomad4 FIN exome AF: 0.473

Gnomad4 NFE exome AF: 0.444

Gnomad4 OTH exome AF: 0.432

GnomAD4 genome AF: 0.443 AC: 67268 AN: 152010 Hom.: 15107 Cov.: 32 AF XY: 0.440 AC XY: 32685 AN XY: 74288

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.401

Alfa AF: 0.458 Hom.: 1980

Bravo AF: 0.435

Asia WGS AF: 0.378 AC: 1312 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.70
DANN	Benign	0.84

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: rs4705375; hg19: chr5-149151448;