rs1556206910

chrX-120541639-ACT-A

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PP5_Moderate

The NM_001079872.2(CUL4B):c.1404_1405del(p.Val469SerfsTer21) variant causes a frameshift change. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 23)
• Consequence: CUL4B NM_001079872.2 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.08

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant X-120541639-ACT-A is Pathogenic according to our data. Variant chrX-120541639-ACT-A is described in ClinVar as [Pathogenic]. Clinvar id is 523617.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.1404_1405del	p.Val469SerfsTer21	frameshift_variant	10/20	ENST00000371322.11
CUL4B	NM_001330624.2	c.1419_1420del	p.Val474SerfsTer21	frameshift_variant	11/21
CUL4B	NM_001369145.1	c.870_871del	p.Val291SerfsTer21	frameshift_variant	10/20
CUL4B	NM_003588.4	c.1458_1459del	p.Val487SerfsTer21	frameshift_variant	12/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUL4B	ENST00000371322.11	c.1404_1405del	p.Val469SerfsTer21	frameshift_variant	10/20	1	NM_001079872.2

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

X-linked intellectual disability Cabezas type Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Center of Genomic medicine, Geneva, University Hospital of Geneva

Jun 19, 2017

This hemizygous variant in the CUL4B gene was identified in a young patient with developmental disorder. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1556206910; hg19: chrX-119675494;