X-120530154-CTAAG-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_001079872.2(CUL4B):c.2536_2539delCTTA(p.Leu846AlafsTer13) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001079872.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CUL4B | NM_001079872.2 | c.2536_2539delCTTA | p.Leu846AlafsTer13 | frameshift_variant | Exon 19 of 20 | ENST00000371322.11 | NP_001073341.1 | |
CUL4B | NM_003588.4 | c.2590_2593delCTTA | p.Leu864AlafsTer13 | frameshift_variant | Exon 21 of 22 | NP_003579.3 | ||
CUL4B | NM_001330624.2 | c.2551_2554delCTTA | p.Leu851AlafsTer13 | frameshift_variant | Exon 20 of 21 | NP_001317553.1 | ||
CUL4B | NM_001369145.1 | c.2002_2005delCTTA | p.Leu668AlafsTer13 | frameshift_variant | Exon 19 of 20 | NP_001356074.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CUL4B | ENST00000371322.11 | c.2536_2539delCTTA | p.Leu846AlafsTer13 | frameshift_variant | Exon 19 of 20 | 1 | NM_001079872.2 | ENSP00000360373.5 | ||
CUL4B | ENST00000681206.1 | c.2650_2653delCTTA | p.Leu884AlafsTer13 | frameshift_variant | Exon 22 of 23 | ENSP00000505480.1 | ||||
CUL4B | ENST00000680673.1 | c.2590_2593delCTTA | p.Leu864AlafsTer13 | frameshift_variant | Exon 21 of 22 | ENSP00000505084.1 | ||||
CUL4B | ENST00000681253.1 | c.2590_2593delCTTA | p.Leu864AlafsTer13 | frameshift_variant | Exon 22 of 23 | ENSP00000506259.1 | ||||
CUL4B | ENST00000681652.1 | c.2590_2593delCTTA | p.Leu864AlafsTer13 | frameshift_variant | Exon 24 of 25 | ENSP00000505176.1 | ||||
CUL4B | ENST00000336592.11 | c.2551_2554delCTTA | p.Leu851AlafsTer13 | frameshift_variant | Exon 20 of 21 | 5 | ENSP00000338919.6 | |||
CUL4B | ENST00000674137.11 | c.2542_2545delCTTA | p.Leu848AlafsTer13 | frameshift_variant | Exon 19 of 20 | ENSP00000501019.6 | ||||
CUL4B | ENST00000681090.1 | c.2443_2446delCTTA | p.Leu815AlafsTer13 | frameshift_variant | Exon 19 of 20 | ENSP00000506288.1 | ||||
CUL4B | ENST00000679927.1 | c.2191_2194delCTTA | p.Leu731AlafsTer13 | frameshift_variant | Exon 20 of 21 | ENSP00000505603.1 | ||||
CUL4B | ENST00000371323.3 | c.2002_2005delCTTA | p.Leu668AlafsTer13 | frameshift_variant | Exon 19 of 20 | 5 | ENSP00000360374.3 | |||
CUL4B | ENST00000680474.1 | c.1978_1981delCTTA | p.Leu660fs | frameshift_variant | Exon 18 of 20 | ENSP00000505562.1 | ||||
CUL4B | ENST00000679844.1 | c.1873_1876delCTTA | p.Leu625fs | frameshift_variant | Exon 17 of 18 | ENSP00000505239.1 | ||||
CUL4B | ENST00000404115.8 | c.2439+2264_2439+2267delCTTA | intron_variant | Intron 18 of 18 | 1 | ENSP00000384109.4 | ||||
CUL4B | ENST00000673919.1 | n.*1983_*1986delCTTA | non_coding_transcript_exon_variant | Exon 20 of 21 | ENSP00000500994.1 | |||||
CUL4B | ENST00000674073.2 | n.*92_*95delCTTA | non_coding_transcript_exon_variant | Exon 17 of 18 | ENSP00000501262.2 | |||||
CUL4B | ENST00000679405.1 | n.*1745_*1748delCTTA | non_coding_transcript_exon_variant | Exon 21 of 22 | ENSP00000504985.1 | |||||
CUL4B | ENST00000679432.1 | n.*1745_*1748delCTTA | non_coding_transcript_exon_variant | Exon 21 of 22 | ENSP00000505343.1 | |||||
CUL4B | ENST00000680918.1 | n.*1452_*1455delCTTA | non_coding_transcript_exon_variant | Exon 17 of 18 | ENSP00000505955.1 | |||||
CUL4B | ENST00000681080.1 | n.*1745_*1748delCTTA | non_coding_transcript_exon_variant | Exon 19 of 20 | ENSP00000505898.1 | |||||
CUL4B | ENST00000681189.1 | n.*702_*705delCTTA | non_coding_transcript_exon_variant | Exon 19 of 20 | ENSP00000505973.1 | |||||
CUL4B | ENST00000681333.1 | n.*3429_*3432delCTTA | non_coding_transcript_exon_variant | Exon 16 of 17 | ENSP00000505739.1 | |||||
CUL4B | ENST00000681908.1 | n.*708_*711delCTTA | non_coding_transcript_exon_variant | Exon 19 of 20 | ENSP00000505777.1 | |||||
CUL4B | ENST00000673919.1 | n.*1983_*1986delCTTA | 3_prime_UTR_variant | Exon 20 of 21 | ENSP00000500994.1 | |||||
CUL4B | ENST00000674073.2 | n.*92_*95delCTTA | 3_prime_UTR_variant | Exon 17 of 18 | ENSP00000501262.2 | |||||
CUL4B | ENST00000679405.1 | n.*1745_*1748delCTTA | 3_prime_UTR_variant | Exon 21 of 22 | ENSP00000504985.1 | |||||
CUL4B | ENST00000679432.1 | n.*1745_*1748delCTTA | 3_prime_UTR_variant | Exon 21 of 22 | ENSP00000505343.1 | |||||
CUL4B | ENST00000680918.1 | n.*1452_*1455delCTTA | 3_prime_UTR_variant | Exon 17 of 18 | ENSP00000505955.1 | |||||
CUL4B | ENST00000681080.1 | n.*1745_*1748delCTTA | 3_prime_UTR_variant | Exon 19 of 20 | ENSP00000505898.1 | |||||
CUL4B | ENST00000681189.1 | n.*702_*705delCTTA | 3_prime_UTR_variant | Exon 19 of 20 | ENSP00000505973.1 | |||||
CUL4B | ENST00000681333.1 | n.*3429_*3432delCTTA | 3_prime_UTR_variant | Exon 16 of 17 | ENSP00000505739.1 | |||||
CUL4B | ENST00000681908.1 | n.*708_*711delCTTA | 3_prime_UTR_variant | Exon 19 of 20 | ENSP00000505777.1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Frameshift variant predicted to result in abnormal protein length as the last 50 amino acid(s) are replaced with 12 different amino acid(s), and other similar variants have been reported in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25385192) -
CUL4B-related disorder Other:1
Variant interpreted as Likely pathogenic and reported on 10-13-2018 by GeneDx. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Philip Payne PhD, FACMI from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at