rs754330779
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP3PP5BP3BS2
The NM_001079872.2(CUL4B):c.369_377delCTCCTCCTC(p.Ser124_Ser126del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,208,215 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001079872.2 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CUL4B | NM_001079872.2 | c.369_377delCTCCTCCTC | p.Ser124_Ser126del | disruptive_inframe_deletion | Exon 1 of 20 | ENST00000371322.11 | NP_001073341.1 | |
CUL4B | NM_003588.4 | c.423_431delCTCCTCCTC | p.Ser142_Ser144del | disruptive_inframe_deletion | Exon 3 of 22 | NP_003579.3 | ||
CUL4B | NM_001330624.2 | c.384_392delCTCCTCCTC | p.Ser129_Ser131del | disruptive_inframe_deletion | Exon 2 of 21 | NP_001317553.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CUL4B | ENST00000371322.11 | c.369_377delCTCCTCCTC | p.Ser124_Ser126del | disruptive_inframe_deletion | Exon 1 of 20 | 1 | NM_001079872.2 | ENSP00000360373.5 | ||
CUL4B | ENST00000681206.1 | c.384_392delCTCCTCCTC | p.Ser129_Ser131del | disruptive_inframe_deletion | Exon 2 of 23 | ENSP00000505480.1 | ||||
CUL4B | ENST00000680673.1 | c.423_431delCTCCTCCTC | p.Ser142_Ser144del | disruptive_inframe_deletion | Exon 3 of 22 | ENSP00000505084.1 | ||||
CUL4B | ENST00000681253.1 | c.423_431delCTCCTCCTC | p.Ser142_Ser144del | disruptive_inframe_deletion | Exon 4 of 23 | ENSP00000506259.1 | ||||
CUL4B | ENST00000681652.1 | c.423_431delCTCCTCCTC | p.Ser142_Ser144del | disruptive_inframe_deletion | Exon 6 of 25 | ENSP00000505176.1 | ||||
CUL4B | ENST00000336592.11 | c.384_392delCTCCTCCTC | p.Ser129_Ser131del | disruptive_inframe_deletion | Exon 2 of 21 | 5 | ENSP00000338919.6 | |||
CUL4B | ENST00000674137.11 | c.369_377delCTCCTCCTC | p.Ser124_Ser126del | disruptive_inframe_deletion | Exon 1 of 20 | ENSP00000501019.6 | ||||
CUL4B | ENST00000681090.1 | c.369_377delCTCCTCCTC | p.Ser124_Ser126del | disruptive_inframe_deletion | Exon 1 of 20 | ENSP00000506288.1 | ||||
CUL4B | ENST00000404115.8 | c.369_377delCTCCTCCTC | p.Ser124_Ser126del | disruptive_inframe_deletion | Exon 1 of 19 | 1 | ENSP00000384109.4 | |||
CUL4B | ENST00000679927.1 | c.24_32delCTCCTCCTC | p.Ser9_Ser11del | disruptive_inframe_deletion | Exon 2 of 21 | ENSP00000505603.1 | ||||
CUL4B | ENST00000673919.1 | n.369_377delCTCCTCCTC | non_coding_transcript_exon_variant | Exon 1 of 21 | ENSP00000500994.1 | |||||
CUL4B | ENST00000679432.1 | n.354_362delCTCCTCCTC | non_coding_transcript_exon_variant | Exon 1 of 22 | ENSP00000505343.1 | |||||
CUL4B | ENST00000681333.1 | n.369_377delCTCCTCCTC | non_coding_transcript_exon_variant | Exon 1 of 17 | ENSP00000505739.1 |
Frequencies
GnomAD3 genomes AF: 0.0000631 AC: 7AN: 111015Hom.: 0 Cov.: 22 AF XY: 0.0000300 AC XY: 1AN XY: 33341
GnomAD3 exomes AF: 0.0000231 AC: 4AN: 173145Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 61627
GnomAD4 exome AF: 0.0000428 AC: 47AN: 1097200Hom.: 0 AF XY: 0.0000413 AC XY: 15AN XY: 362924
GnomAD4 genome AF: 0.0000631 AC: 7AN: 111015Hom.: 0 Cov.: 22 AF XY: 0.0000300 AC XY: 1AN XY: 33341
ClinVar
Submissions by phenotype
not provided Pathogenic:1
The c.423_431delCTCCTCCTC variant in the XXX gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.423_431delCTCCTCCTC variant causes an inframe deletion of three amino acids starting at Serine 144, denoted p.S144_S146del. The c.423_431delCTCCTCCTC variant is observed in 5/86720 (0.0058%) alleles from individuals of non-Finnish European background, and 5/190079 total alleles in large population cohorts (Lek et al., 2016). We interpret c.423_431delCTCCTCCTC as a likely pathogenic variant. -
X-linked intellectual disability Cabezas type Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant, c.423_431del, results in the deletion of 3 amino acid(s) of the CUL4B protein (p.Ser144_Ser146del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs756411375, ExAC 0.004%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals with CUL4B-related conditions. ClinVar contains an entry for this variant (Variation ID: 504176). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. -
CUL4B-related disorder Uncertain:1
The CUL4B c.423_431del9 variant is predicted to result in an in-frame deletion (p.Ser144_Ser146del). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0057% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at