rs7172
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002796.3(PSMB4):c.75G>A(p.Pro25=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 1,613,768 control chromosomes in the GnomAD database, including 485,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.64 ( 34866 hom., cov: 31)
Exomes 𝑓: 0.77 ( 450308 hom. )
Consequence
PSMB4
NM_002796.3 synonymous
NM_002796.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0750
Genes affected
PSMB4 (HGNC:9541): (proteasome 20S subunit beta 4) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 1-151399662-G-A is Benign according to our data. Variant chr1-151399662-G-A is described in ClinVar as [Benign]. Clinvar id is 1165733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.075 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSMB4 | NM_002796.3 | c.75G>A | p.Pro25= | synonymous_variant | 1/7 | ENST00000290541.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSMB4 | ENST00000290541.7 | c.75G>A | p.Pro25= | synonymous_variant | 1/7 | 1 | NM_002796.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.643 AC: 97600AN: 151854Hom.: 34862 Cov.: 31
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GnomAD3 exomes AF: 0.665 AC: 167147AN: 251210Hom.: 61538 AF XY: 0.688 AC XY: 93534AN XY: 135868
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GnomAD4 exome AF: 0.771 AC: 1127646AN: 1461796Hom.: 450308 Cov.: 63 AF XY: 0.772 AC XY: 561664AN XY: 727202
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GnomAD4 genome ? AF: 0.642 AC: 97624AN: 151972Hom.: 34866 Cov.: 31 AF XY: 0.638 AC XY: 47360AN XY: 74288
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 29, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Nov 12, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 79% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. - |
PSMB4-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 17, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Proteasome-associated autoinflammatory syndrome 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Oct 25, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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