rs1387389

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002585.4(PBX1):​c.266-71969G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,960 control chromosomes in the GnomAD database, including 10,612 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 0.36 ( 10612 hom., cov: 32)

Consequence

PBX1
NM_002585.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0970
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PBX1NM_002585.4 linkuse as main transcriptc.266-71969G>A intron_variant ENST00000420696.7 NP_002576.1 P40424-1A1MJ41A8K5V0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PBX1ENST00000420696.7 linkuse as main transcriptc.266-71969G>A intron_variant 1 NM_002585.4 ENSP00000405890.2 P40424-1

Frequencies

GnomAD3 genomes
AF:
0.363
AC:
55179
AN:
151842
Hom.:
10597
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.435
Gnomad AMI
AF:
0.273
Gnomad AMR
AF:
0.285
Gnomad ASJ
AF:
0.310
Gnomad EAS
AF:
0.568
Gnomad SAS
AF:
0.528
Gnomad FIN
AF:
0.296
Gnomad MID
AF:
0.266
Gnomad NFE
AF:
0.326
Gnomad OTH
AF:
0.329
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.363
AC:
55210
AN:
151960
Hom.:
10612
Cov.:
32
AF XY:
0.365
AC XY:
27123
AN XY:
74236
show subpopulations
Gnomad4 AFR
AF:
0.435
Gnomad4 AMR
AF:
0.284
Gnomad4 ASJ
AF:
0.310
Gnomad4 EAS
AF:
0.568
Gnomad4 SAS
AF:
0.529
Gnomad4 FIN
AF:
0.296
Gnomad4 NFE
AF:
0.326
Gnomad4 OTH
AF:
0.332
Alfa
AF:
0.343
Hom.:
4202
Bravo
AF:
0.365
Asia WGS
AF:
0.507
AC:
1765
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
CADD
Benign
3.1
DANN
Benign
0.76

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1387389; hg19: chr1-164689762; API