CUL4B p.Cys619Cys

Variant names:

• chrX-120538204-C-C
• NM_001079872.2:c.

Your query was ambiguous. Multiple possible variants found:

• chrX-120538205--
• chrX-120538205-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001079872.2(CUL4B):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: CUL4B NM_001079872.2 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 0 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 type

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079872.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4B	NM_001079872.2	MANE Select	c.		exon_region	Exon 14 of 20	NP_001073341.1	Q13620-1
	CUL4B	NM_003588.4		c.		exon_region	Exon 16 of 22	NP_003579.3
	CUL4B	NM_001330624.2		c.		exon_region	Exon 15 of 21	NP_001317553.1	K4DI93

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4B	ENST00000371322.11	TSL:1 MANE Select	c.		exon_region	Exon 14 of 20	ENSP00000360373.5	Q13620-1
	CUL4B	ENST00000681206.1		c.		exon_region	Exon 17 of 23	ENSP00000505480.1	A0A7P0T954
	CUL4B	ENST00000680673.1		c.		exon_region	Exon 16 of 22	ENSP00000505084.1	Q13620-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-119672059;