chrX-120560261-T-TGAGGAG
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3
The NM_001079872.2(CUL4B):c.372_377dupCTCCTC(p.Ser125_Ser126dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00000901 in 111,015 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S126S) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)
Consequence
CUL4B
NM_001079872.2 disruptive_inframe_insertion
NM_001079872.2 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.84
Publications
1 publications found
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]
CUL4B Gene-Disease associations (from GenCC):
- X-linked intellectual disability, Cabezas typeInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_001079872.2
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CUL4B | NM_001079872.2 | c.372_377dupCTCCTC | p.Ser125_Ser126dup | disruptive_inframe_insertion | Exon 1 of 20 | ENST00000371322.11 | NP_001073341.1 | |
| CUL4B | NM_003588.4 | c.426_431dupCTCCTC | p.Ser143_Ser144dup | disruptive_inframe_insertion | Exon 3 of 22 | NP_003579.3 | ||
| CUL4B | NM_001330624.2 | c.387_392dupCTCCTC | p.Ser130_Ser131dup | disruptive_inframe_insertion | Exon 2 of 21 | NP_001317553.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CUL4B | ENST00000371322.11 | c.372_377dupCTCCTC | p.Ser125_Ser126dup | disruptive_inframe_insertion | Exon 1 of 20 | 1 | NM_001079872.2 | ENSP00000360373.5 | ||
| CUL4B | ENST00000681206.1 | c.387_392dupCTCCTC | p.Ser130_Ser131dup | disruptive_inframe_insertion | Exon 2 of 23 | ENSP00000505480.1 | ||||
| CUL4B | ENST00000680673.1 | c.426_431dupCTCCTC | p.Ser143_Ser144dup | disruptive_inframe_insertion | Exon 3 of 22 | ENSP00000505084.1 | ||||
| CUL4B | ENST00000681253.1 | c.426_431dupCTCCTC | p.Ser143_Ser144dup | disruptive_inframe_insertion | Exon 4 of 23 | ENSP00000506259.1 | ||||
| CUL4B | ENST00000681652.1 | c.426_431dupCTCCTC | p.Ser143_Ser144dup | disruptive_inframe_insertion | Exon 6 of 25 | ENSP00000505176.1 | ||||
| CUL4B | ENST00000336592.11 | c.387_392dupCTCCTC | p.Ser130_Ser131dup | disruptive_inframe_insertion | Exon 2 of 21 | 5 | ENSP00000338919.6 | |||
| CUL4B | ENST00000674137.11 | c.372_377dupCTCCTC | p.Ser125_Ser126dup | disruptive_inframe_insertion | Exon 1 of 20 | ENSP00000501019.6 | ||||
| CUL4B | ENST00000681090.1 | c.372_377dupCTCCTC | p.Ser125_Ser126dup | disruptive_inframe_insertion | Exon 1 of 20 | ENSP00000506288.1 | ||||
| CUL4B | ENST00000404115.8 | c.372_377dupCTCCTC | p.Ser125_Ser126dup | disruptive_inframe_insertion | Exon 1 of 19 | 1 | ENSP00000384109.4 | |||
| CUL4B | ENST00000679927.1 | c.27_32dupCTCCTC | p.Ser10_Ser11dup | disruptive_inframe_insertion | Exon 2 of 21 | ENSP00000505603.1 | ||||
| CUL4B | ENST00000673919.1 | n.372_377dupCTCCTC | non_coding_transcript_exon_variant | Exon 1 of 21 | ENSP00000500994.1 | |||||
| CUL4B | ENST00000679432.1 | n.357_362dupCTCCTC | non_coding_transcript_exon_variant | Exon 1 of 22 | ENSP00000505343.1 | |||||
| CUL4B | ENST00000681333.1 | n.372_377dupCTCCTC | non_coding_transcript_exon_variant | Exon 1 of 17 | ENSP00000505739.1 |
Frequencies
GnomAD3 genomes 0.00000901 AC: 1AN: 111015Hom.: 0 Cov.: 22 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
111015
Hom.:
Cov.:
22
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
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Gnomad SAS
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome 0.00000901 AC: 1AN: 111015Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33341 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
111015
Hom.:
Cov.:
22
AF XY:
AC XY:
0
AN XY:
33341
show subpopulations
African (AFR)
AF:
AC:
0
AN:
30539
American (AMR)
AF:
AC:
0
AN:
10437
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2637
East Asian (EAS)
AF:
AC:
0
AN:
3537
South Asian (SAS)
AF:
AC:
0
AN:
2654
European-Finnish (FIN)
AF:
AC:
1
AN:
5898
Middle Eastern (MID)
AF:
AC:
0
AN:
237
European-Non Finnish (NFE)
AF:
AC:
0
AN:
52899
Other (OTH)
AF:
AC:
0
AN:
1493
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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