5-149771885-A-T

Variant names:

• chr5-149771885-A-T
• rs4705375
• NM_133263.4:c.78+41465A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.81).
• BP6: Variant 5-149771885-A-T is Benign according to our data. Variant chr5-149771885-A-T is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133263.4. 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+41465A>T		intron	N/A	NP_573570.3
	PPARGC1B	NM_001172698.2		c.78+41465A>T		intron	N/A	NP_001166169.1	Q86YN6-5
	PPARGC1B	NM_001172699.2		c.-252A>T		upstream_gene	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+41465A>T		intron	N/A	ENSP00000312649.5	Q86YN6-1
	PPARGC1B	ENST00000394320.7	TSL:1	c.78+41465A>T		intron	N/A	ENSP00000377855.3	Q86YN6-3
	PPARGC1B	ENST00000360453.8	TSL:1	c.78+41465A>T		intron	N/A	ENSP00000353638.4	Q86YN6-5

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

African (AFR) AF: 0.474 AC: 5713 AN: 12044

American (AMR) AF: 0.354 AC: 3743 AN: 10564

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 4967 AN: 11418

East Asian (EAS) AF: 0.312 AC: 6620 AN: 21234

South Asian (SAS) AF: 0.364 AC: 11608 AN: 31886

European-Finnish (FIN) AF: 0.473 AC: 11016 AN: 23274

Middle Eastern (MID) AF: 0.406 AC: 804 AN: 1980

European-Non Finnish (NFE) AF: 0.444 AC: 175905 AN: 396166

Other (OTH) AF: 0.432 AC: 11201 AN: 25910

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

African (AFR) AF: 0.480 AC: 19883 AN: 41444

American (AMR) AF: 0.379 AC: 5790 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1565 AN: 3468

East Asian (EAS) AF: 0.334 AC: 1725 AN: 5162

South Asian (SAS) AF: 0.364 AC: 1761 AN: 4832

European-Finnish (FIN) AF: 0.480 AC: 5071 AN: 10562

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30113 AN: 67954

Other (OTH) AF: 0.401 AC: 846 AN: 2108

Alfa AF: 0.458 Hom.: 1980

Bravo AF: 0.435

Asia WGS AF: 0.378 AC: 1312 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.81
CADD	Benign	0.70
DANN	Benign	0.84
PhyloP100		-0.25
PromoterAI		0.23	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4705375; hg19: chr5-149151448;