dbSNP rs12723035: PBX1:c.*4249A>G (chr1-164850925-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002585.4(PBX1):c.*4249A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 211,450 control chromosomes in the GnomAD database, including 14,680 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 0.37 ( 11103 hom., cov: 32)

Exomes 𝑓: 0.34 ( 3577 hom. )

Consequence

PBX1
NM_002585.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.498

Publications

6 publications found

Variant links:

Genes affected

PBX1 (HGNC:8632): (PBX homeobox 1) This gene encodes a nuclear protein that belongs to the PBX homeobox family of transcriptional factors. Studies in mice suggest that this gene may be involved in the regulation of osteogenesis and required for skeletal patterning and programming. A chromosomal translocation, t(1;19) involving this gene and TCF3/E2A gene, is associated with pre-B-cell acute lymphoblastic leukemia. The resulting fusion protein, in which the DNA binding domain of E2A is replaced by the DNA binding domain of this protein, transforms cells by constitutively activating transcription of genes regulated by the PBX protein family. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2017]

PBX1 Gene-Disease associations (from GenCC):

congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Illumina, PanelApp Australia

PBX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBX1	NM_002585.4 link	c.*4249A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000420696.7	NP_002576.1	P40424-1A1MJ41A8K5V0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PBX1	ENST00000420696.7 link	c.*4249A>G	3_prime_UTR_variant	Exon 9 of 9	1	NM_002585.4	ENSP00000405890.2	P40424-1
PBX1	ENST00000699845.1 link	c.*43+29299A>G	intron_variant	Intron 7 of 7			ENSP00000514643.1	P40424-2
PBX1	ENST00000699848.1 link	c.756+29299A>G	intron_variant	Intron 6 of 6			ENSP00000514646.1	A0A8V8TPF7
PBX1	ENST00000558796.2 link	n.257+19442A>G	intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56365

AN:

151870

Hom.:

11073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.440

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.379

GnomAD4 exome

AF:

0.337

AC:

20009

AN:

59462

Hom.:

3577

Cov.:

AF XY:

0.340

AC XY:

9343

AN XY:

27478

show subpopulations

African (AFR)

AF:

0.497

AC:

1337

AN:

2692

American (AMR)

AF:

0.248

AC:

439

AN:

1772

Ashkenazi Jewish (ASJ)

AF:

0.426

AC:

1608

AN:

3774

East Asian (EAS)

AF:

0.218

AC:

1969

AN:

9026

South Asian (SAS)

AF:

0.382

AC:

191

AN:

500

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AF:

0.380

AC:

140

AN:

368

European-Non Finnish (NFE)

AF:

0.344

AC:

12505

AN:

36318

Other (OTH)

AF:

0.363

AC:

1804

AN:

4964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

670

1341

2011

2682

3352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.371

AC:

56447

AN:

151988

Hom.:

11103

Cov.:

AF XY:

0.371

AC XY:

27551

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.491

AC:

20342

AN:

41404

American (AMR)

AF:

0.284

AC:

4333

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

1526

AN:

3468

East Asian (EAS)

AF:

0.220

AC:

1134

AN:

5154

South Asian (SAS)

AF:

0.376

AC:

1815

AN:

4822

European-Finnish (FIN)

AF:

0.351

AC:

3705

AN:

10570

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.327

AC:

22246

AN:

67992

Other (OTH)

AF:

0.383

AC:

805

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1778

3557

5335

7114

8892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.360

Hom.:

4228

Bravo

AF:

0.367

Asia WGS

AF:

0.336

AC:

1166

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.36

(source)

DANN

Benign

0.36

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over