chr1-164559900-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002585.4(PBX1):c.78G>A(p.Leu26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,550,434 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00083 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000079 ( 1 hom. )
Consequence
PBX1
NM_002585.4 synonymous
NM_002585.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.24
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 1-164559900-G-A is Benign according to our data. Variant chr1-164559900-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2073241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000828 (126/152258) while in subpopulation AFR AF= 0.00296 (123/41578). AF 95% confidence interval is 0.00253. There are 0 homozygotes in gnomad4. There are 54 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 127 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PBX1 | NM_002585.4 | c.78G>A | p.Leu26= | synonymous_variant | 1/9 | ENST00000420696.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PBX1 | ENST00000420696.7 | c.78G>A | p.Leu26= | synonymous_variant | 1/9 | 1 | NM_002585.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000835 AC: 127AN: 152148Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000202 AC: 31AN: 153202Hom.: 1 AF XY: 0.000135 AC XY: 11AN XY: 81358
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GnomAD4 exome AF: 0.0000794 AC: 111AN: 1398176Hom.: 1 Cov.: 35 AF XY: 0.0000769 AC XY: 53AN XY: 689594
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GnomAD4 genome ? AF: 0.000828 AC: 126AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.000725 AC XY: 54AN XY: 74434
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
PBX1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 31, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 13, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at