rs1556200443
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePP3_ModeratePP5_Moderate
The NM_001079872.2(CUL4B):c.1852+1del variant causes a splice donor change involving the alteration of a conserved nucleotide. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Consequence
CUL4B
NM_001079872.2 splice_donor
NM_001079872.2 splice_donor
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.88
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 Likely_pathogenic. Variant got 6 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.04092262 fraction of the gene. Cryptic splice site detected, with MaxEntScore 4.9, offset of 0 (no position change), new splice context is: catGTaggt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant X-120538658-AC-A is Pathogenic according to our data. Variant chrX-120538658-AC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 521673.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUL4B | NM_001079872.2 | c.1852+1del | splice_donor_variant | ENST00000371322.11 | |||
CUL4B | NM_001330624.2 | c.1867+1del | splice_donor_variant | ||||
CUL4B | NM_001369145.1 | c.1318+1del | splice_donor_variant | ||||
CUL4B | NM_003588.4 | c.1906+1del | splice_donor_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUL4B | ENST00000371322.11 | c.1852+1del | splice_donor_variant | 1 | NM_001079872.2 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 20
GnomAD4 exome
Cov.:
20
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 24, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 3
DS_DL_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at