rs2275558

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_002585.4(PBX1):c.61G>A(p.Gly21Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,550,066 control chromosomes in the GnomAD database, including 51,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 4494 hom., cov: 31)

Exomes 𝑓: 0.24 ( 47454 hom. )

Consequence

PBX1
NM_002585.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 8.01

Publications

44 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 -19 ACMG points.

PP2

Missense variant in the PBX1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 15 curated pathogenic missense variants (we use a threshold of 10). The gene has 3 curated benign missense variants. Gene score misZ: 3.8266 (above the threshold of 3.09). Trascript score misZ: 4.2973 (above the threshold of 3.09). GenCC associations: The gene is linked to congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay.

BP4

Computational evidence support a benign effect (MetaRNN=2.8911233E-4).

BP6

Variant 1-164559883-G-A is Benign according to our data. Variant chr1-164559883-G-A is described in ClinVar as Benign. ClinVar VariationId is 1288942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBX1	NM_002585.4 link	c.61G>A	p.Gly21Ser	missense_variant	Exon 1 of 9	ENST00000420696.7	NP_002576.1	P40424-1A1MJ41A8K5V0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBX1	ENST00000420696.7 link	c.61G>A	p.Gly21Ser	missense_variant	Exon 1 of 9	1	NM_002585.4	ENSP00000405890.2		P40424-1

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

30976

AN:

151828

Hom.:

4492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0447

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.631

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.211

GnomAD2 exomes

AF:

0.304

AC:

46889

AN:

154030

AF XY:

0.304

show subpopulations

Gnomad AFR exome

AF:

0.0372

Gnomad AMR exome

AF:

0.477

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.632

Gnomad FIN exome

AF:

0.208

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.241

AC:

336771

AN:

1398128

Hom.:

47454

Cov.:

AF XY:

0.245

AC XY:

168880

AN XY:

689538

show subpopulations

African (AFR)

AF:

0.0357

AC:

1127

AN:

31558

American (AMR)

AF:

0.466

AC:

16585

AN:

35624

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

6111

AN:

25154

East Asian (EAS)

AF:

0.679

AC:

24163

AN:

35606

South Asian (SAS)

AF:

0.376

AC:

29793

AN:

79148

European-Finnish (FIN)

AF:

0.207

AC:

10169

AN:

49220

Middle Eastern (MID)

AF:

0.179

AC:

971

AN:

5436

European-Non Finnish (NFE)

AF:

0.217

AC:

233695

AN:

1078478

Other (OTH)

AF:

0.244

AC:

14157

AN:

57904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

12094

24188

36281

48375

60469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8366

16732

25098

33464

41830

<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:

0.204

AC:

30981

AN:

151938

Hom.:

4494

Cov.:

AF XY:

0.213

AC XY:

15845

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.0446

AC:

1854

AN:

41530

American (AMR)

AF:

0.360

AC:

5499

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

812

AN:

3466

East Asian (EAS)

AF:

0.632

AC:

3212

AN:

5080

South Asian (SAS)

AF:

0.378

AC:

1814

AN:

4796

European-Finnish (FIN)

AF:

0.212

AC:

2243

AN:

10558

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14785

AN:

67944

Other (OTH)

AF:

0.211

AC:

443

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1058

2116

3174

4232

5290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.230

Hom.:

8688

Bravo

AF:

0.209

TwinsUK

AF:

0.218

AC:

808

ALSPAC

AF:

0.214

AC:

825

ESP6500AA

AF:

0.0408

AC:

168

ESP6500EA

AF:

0.188

AC:

1503

ExAC

AF:

0.171

AC:

12421

Asia WGS

AF:

0.448

AC:

1555

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 31934099) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;T;T;.;.;T

Eigen

Benign

-0.011

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.81

T;T;T;T;T;T

MetaRNN

Benign

0.00029

T;T;T;T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.0

.;.;L;L;L;.

PhyloP100

8.0

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.9

.;N;N;.;N;N

REVEL

Uncertain

0.31

Sift

Benign

0.12

.;T;T;.;T;T

Sift4G

Benign

0.083

T;T;T;T;T;T

Polyphen

0.49

.;.;P;.;.;.

Vest4

0.43

MPC

0.050

ClinPred

0.043

GERP RS

5.2

PromoterAI

-0.070

Neutral

(source)

Varity_R

0.12

gMVP

0.46

Mutation Taster

=97/3

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over