chrX-120560261-T-TGAG
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3BP6BS2
The NM_001079872.2(CUL4B):c.377_378insCTC(p.Ser127dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.0000306 in 1,208,157 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S126S) has been classified as Likely benign.
Frequency
Consequence
NM_001079872.2 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUL4B | NM_001079872.2 | c.377_378insCTC | p.Ser127dup | inframe_insertion | 1/20 | ENST00000371322.11 | |
CUL4B | NM_001330624.2 | c.392_393insCTC | p.Ser132dup | inframe_insertion | 2/21 | ||
CUL4B | NM_003588.4 | c.431_432insCTC | p.Ser145dup | inframe_insertion | 3/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUL4B | ENST00000371322.11 | c.377_378insCTC | p.Ser127dup | inframe_insertion | 1/20 | 1 | NM_001079872.2 |
Frequencies
GnomAD3 genomes AF: 0.0000540 AC: 6AN: 111014Hom.: 0 Cov.: 22 AF XY: 0.0000600 AC XY: 2AN XY: 33340
GnomAD3 exomes AF: 0.0000404 AC: 7AN: 173145Hom.: 0 AF XY: 0.0000325 AC XY: 2AN XY: 61627
GnomAD4 exome AF: 0.0000283 AC: 31AN: 1097143Hom.: 0 Cov.: 33 AF XY: 0.0000220 AC XY: 8AN XY: 362877
GnomAD4 genome AF: 0.0000540 AC: 6AN: 111014Hom.: 0 Cov.: 22 AF XY: 0.0000600 AC XY: 2AN XY: 33340
ClinVar
Submissions by phenotype
CUL4B-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 31, 2023 | The CUL4B c.429_431dupCTC variant is predicted to result in an in-frame duplication (p.Ser146dup). This variant was reported in an individual with intellectual disability and additional features consistent with CUL4B-related disease (Tzschach et al 2015. PubMed ID: 25649377). This variant is reported in 0.014% of alleles in individuals of East Asian descent in gnomAD, including three hemizygotes (http://gnomad.broadinstitute.org/variant/X-119694116-T-TGAG). The gnomAD data suggest it is less likely that this is a pathogenic variant. However, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 01, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
X-linked intellectual disability Cabezas type Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 16, 2023 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 06, 2017 | This alteration is classified as likely 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at