X-120538205-G-A
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001079872.2(CUL4B):c.1857C>T(p.Cys619=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,156,497 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 558 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., 36 hem., cov: 23)
Exomes 𝑓: 0.0014 ( 0 hom. 522 hem. )
Consequence
CUL4B
NM_001079872.2 synonymous
NM_001079872.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.73
Genes affected
CUL4B (HGNC:2555): (cullin 4B) This gene is a member of the cullin family. The encoded protein forms a complex that functions as an E3 ubiquitin ligase and catalyzes the polyubiquitination of specific protein substrates in the cell. The protein interacts with a ring finger protein, and is required for the proteolysis of several regulators of DNA replication including chromatin licensing and DNA replication factor 1 and cyclin E. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant X-120538205-G-A is Benign according to our data. Variant chrX-120538205-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 194630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-120538205-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=1.73 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00114 (127/111794) while in subpopulation SAS AF= 0.00476 (13/2730). AF 95% confidence interval is 0.00282. There are 0 homozygotes in gnomad4. There are 36 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 36 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUL4B | NM_001079872.2 | c.1857C>T | p.Cys619= | synonymous_variant | 14/20 | ENST00000371322.11 | |
CUL4B | NM_003588.4 | c.1911C>T | p.Cys637= | synonymous_variant | 16/22 | ||
CUL4B | NM_001330624.2 | c.1872C>T | p.Cys624= | synonymous_variant | 15/21 | ||
CUL4B | NM_001369145.1 | c.1323C>T | p.Cys441= | synonymous_variant | 14/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUL4B | ENST00000371322.11 | c.1857C>T | p.Cys619= | synonymous_variant | 14/20 | 1 | NM_001079872.2 |
Frequencies
GnomAD3 genomes AF: 0.00113 AC: 126AN: 111742Hom.: 0 Cov.: 23 AF XY: 0.00103 AC XY: 35AN XY: 33942
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GnomAD3 exomes AF: 0.00173 AC: 307AN: 177961Hom.: 0 AF XY: 0.00208 AC XY: 131AN XY: 62851
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GnomAD4 exome AF: 0.00139 AC: 1453AN: 1044703Hom.: 0 Cov.: 23 AF XY: 0.00164 AC XY: 522AN XY: 318991
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GnomAD4 genome AF: 0.00114 AC: 127AN: 111794Hom.: 0 Cov.: 23 AF XY: 0.00106 AC XY: 36AN XY: 34004
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
X-linked intellectual disability Cabezas type Benign:3
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 13, 2019 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 08, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 06, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 15, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 06, 2017 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 27, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
CUL4B-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 05, 2022 | 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). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
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