X-120530259-CA-C

Position:

• chrX-120530259-CA-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_001079872.2(CUL4B):​c.2440-6delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: CUL4B NM_001079872.2 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.74

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant X-120530259-CA-C is Benign according to our data. Variant chrX-120530259-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 3358208.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUL4B	NM_001079872.2	c.2440-6delT		splice_region_variant, intron_variant		ENST00000371322.11	NP_001073341.1
CUL4B	NM_003588.4	c.2494-6delT		splice_region_variant, intron_variant			NP_003579.3
CUL4B	NM_001330624.2	c.2455-6delT		splice_region_variant, intron_variant			NP_001317553.1
CUL4B	NM_001369145.1	c.1906-6delT		splice_region_variant, intron_variant			NP_001356074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL4B	ENST00000371322.11	c.2440-6delT		splice_region_variant, intron_variant		1	NM_001079872.2	ENSP00000360373.5
CUL4B	ENST00000681206.1	c.2554-6delT		splice_region_variant, intron_variant				ENSP00000505480.1
CUL4B	ENST00000680673.1	c.2494-6delT		splice_region_variant, intron_variant				ENSP00000505084.1
CUL4B	ENST00000681253.1	c.2494-6delT		splice_region_variant, intron_variant				ENSP00000506259.1
CUL4B	ENST00000681652.1	c.2494-6delT		splice_region_variant, intron_variant				ENSP00000505176.1
CUL4B	ENST00000336592.11	c.2455-6delT		splice_region_variant, intron_variant		5		ENSP00000338919.6
CUL4B	ENST00000674137.11	c.2446-6delT		splice_region_variant, intron_variant				ENSP00000501019.6
CUL4B	ENST00000681090.1	c.2347-6delT		splice_region_variant, intron_variant				ENSP00000506288.1
CUL4B	ENST00000404115.8	c.2439+2162delT		intron_variant		1		ENSP00000384109.4
CUL4B	ENST00000679927.1	c.2095-6delT		splice_region_variant, intron_variant				ENSP00000505603.1
CUL4B	ENST00000371323.3	c.1906-6delT		splice_region_variant, intron_variant		5		ENSP00000360374.3
CUL4B	ENST00000680474.1	c.1882-6delT		splice_region_variant, intron_variant				ENSP00000505562.1
CUL4B	ENST00000679844.1	c.1777-6delT		splice_region_variant, intron_variant				ENSP00000505239.1
CUL4B	ENST00000673919.1	n.*1887-6delT		splice_region_variant, intron_variant				ENSP00000500994.1
CUL4B	ENST00000674073.2	n.1709-6delT		splice_region_variant, intron_variant				ENSP00000501262.2
CUL4B	ENST00000679405.1	n.*1649-6delT		splice_region_variant, intron_variant				ENSP00000504985.1
CUL4B	ENST00000679432.1	n.*1649-6delT		splice_region_variant, intron_variant				ENSP00000505343.1
CUL4B	ENST00000680918.1	n.*1356-6delT		splice_region_variant, intron_variant				ENSP00000505955.1
CUL4B	ENST00000681080.1	n.*1649-6delT		splice_region_variant, intron_variant				ENSP00000505898.1
CUL4B	ENST00000681189.1	n.*606-6delT		splice_region_variant, intron_variant				ENSP00000505973.1
CUL4B	ENST00000681333.1	n.*3333-6delT		splice_region_variant, intron_variant				ENSP00000505739.1
CUL4B	ENST00000681908.1	n.*612-6delT		splice_region_variant, intron_variant				ENSP00000505777.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1094938 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 360806

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CUL4B-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 16, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1923230266; hg19: chrX-119664114;