X-120529942-GTTT-GTT

Variant names:

• chrX-120529942-GT-G
• rs76254851
• NM_001079872.2:c.2592+159delA

Variant summary

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

The NM_001079872.2(CUL4B):​c.2592+159delA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000029 (0 hom., 1 hem., cov: 0)
• Consequence: CUL4B NM_001079872.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328
• 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, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.2592+159delA		intron	N/A	NP_001073341.1	Q13620-1
	CUL4B	NM_003588.4		c.2646+159delA		intron	N/A	NP_003579.3
	CUL4B	NM_001330624.2		c.2607+159delA		intron	N/A	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.2592+159delA		intron	N/A	ENSP00000360373.5	Q13620-1
	CUL4B	ENST00000681206.1		c.2706+159delA		intron	N/A	ENSP00000505480.1	A0A7P0T954
	CUL4B	ENST00000680673.1		c.2646+159delA		intron	N/A	ENSP00000505084.1	Q13620-2

Frequencies

GnomAD3 genomes AF: 0.0000286 AC: 3 AN: 104833 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000691

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000196

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000286 AC: 3 AN: 104845 Hom.: 0 Cov.: 0 AF XY: 0.0000353 AC XY: 1 AN XY: 28365

African (AFR) AF: 0.0000690 AC: 2 AN: 28988

American (AMR) AF: 0.00 AC: 0 AN: 9647

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2555

East Asian (EAS) AF: 0.00 AC: 0 AN: 3346

South Asian (SAS) AF: 0.00 AC: 0 AN: 2392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4513

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 203

European-Non Finnish (NFE) AF: 0.0000196 AC: 1 AN: 51123

Other (OTH) AF: 0.00 AC: 0 AN: 1413

Alfa AF: 0.00 Hom.: 1659

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.33

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

Other links and lift over

dbSNP: rs76254851; hg19: chrX-119663797;