5-149772144-G-A

Variant names:

• chr5-149772144-G-A
• rs73796250
• NM_133263.4:c.78+41724G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001172699.2(PPARGC1B):​c.3+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 1,605,292 control chromosomes in the GnomAD database, including 6,197 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.081 (545 hom., cov: 32)
  • Exomes 𝑓: 0.083 (5652 hom.)
• Consequence: PPARGC1B NM_001172699.2 splice_region, intron
• Scores: Splicing: ADA: 0.00001460
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.99
• Publications: 4 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=-0.93).
• BP6: Variant 5-149772144-G-A is Benign according to our data. Variant chr5-149772144-G-A is described in ClinVar as Benign. ClinVar VariationId is 1269772.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172699.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1B	NM_133263.4	MANE Select	c.78+41724G>A		intron	N/A	NP_573570.3
	PPARGC1B	NM_001172698.2		c.78+41724G>A		intron	N/A	NP_001166169.1	Q86YN6-5
	PPARGC1B	NM_001172699.2		c.3+5G>A		splice_region intron	N/A	NP_001166170.1	Q86YN6-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1B	ENST00000309241.10	TSL:1 MANE Select	c.78+41724G>A		intron	N/A	ENSP00000312649.5	Q86YN6-1
	PPARGC1B	ENST00000394320.7	TSL:1	c.78+41724G>A		intron	N/A	ENSP00000377855.3	Q86YN6-3
	PPARGC1B	ENST00000360453.8	TSL:1	c.78+41724G>A		intron	N/A	ENSP00000353638.4	Q86YN6-5

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12251 AN: 152158 Hom.: 545 Cov.: 32

Gnomad AFR AF: 0.0657

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.0578

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.0804

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0802

Gnomad OTH AF: 0.0713

GnomAD2 exomes AF: 0.0877 AC: 20060 AN: 228754 AF XY: 0.0919

Gnomad AFR exome AF: 0.0643

Gnomad AMR exome AF: 0.0414

Gnomad ASJ exome AF: 0.0903

Gnomad EAS exome AF: 0.0768

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.0771

Gnomad OTH exome AF: 0.0935

GnomAD4 exome AF: 0.0830 AC: 120636 AN: 1453016 Hom.: 5652 Cov.: 31 AF XY: 0.0858 AC XY: 61901 AN XY: 721704

African (AFR) AF: 0.0704 AC: 2351 AN: 33408

American (AMR) AF: 0.0436 AC: 1900 AN: 43544

Ashkenazi Jewish (ASJ) AF: 0.0919 AC: 2388 AN: 25986

East Asian (EAS) AF: 0.0760 AC: 3002 AN: 39494

South Asian (SAS) AF: 0.153 AC: 12910 AN: 84136

European-Finnish (FIN) AF: 0.149 AC: 7776 AN: 52214

Middle Eastern (MID) AF: 0.0794 AC: 457 AN: 5758

European-Non Finnish (NFE) AF: 0.0764 AC: 84716 AN: 1108358

Other (OTH) AF: 0.0854 AC: 5136 AN: 60118

GnomAD4 genome AF: 0.0805 AC: 12259 AN: 152276 Hom.: 545 Cov.: 32 AF XY: 0.0850 AC XY: 6326 AN XY: 74458

African (AFR) AF: 0.0656 AC: 2726 AN: 41564

American (AMR) AF: 0.0578 AC: 884 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0827 AC: 287 AN: 3470

East Asian (EAS) AF: 0.0808 AC: 419 AN: 5188

South Asian (SAS) AF: 0.157 AC: 754 AN: 4816

European-Finnish (FIN) AF: 0.143 AC: 1520 AN: 10604

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0802 AC: 5457 AN: 68020

Other (OTH) AF: 0.0729 AC: 154 AN: 2112

Alfa AF: 0.0778 Hom.: 307

Bravo AF: 0.0704

Asia WGS AF: 0.115 AC: 401 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.37
PhyloP100		-2.0
PromoterAI		-0.14	Neutral
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000015
dbscSNV1_RF	Benign	0.0
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: rs73796250; hg19: chr5-149151707;