X-120526872-A-G

Variant names:

• chrX-120526872-A-G
• rs1048730072
• NM_001079872.2:c.2593-16T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001079872.2(CUL4B):​c.2593-16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000857 in 933,439 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000086 (0 hom. 1 hem.)
• Consequence: CUL4B NM_001079872.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.12
• 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant X-120526872-A-G is Benign according to our data. Variant chrX-120526872-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3689913.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL4B	NM_001079872.2	c.2593-16T>C		intron_variant	Intron 19 of 19	ENST00000371322.11	NP_001073341.1
CUL4B	NM_003588.4	c.2647-16T>C		intron_variant	Intron 21 of 21		NP_003579.3
CUL4B	NM_001330624.2	c.2608-16T>C		intron_variant	Intron 20 of 20		NP_001317553.1
CUL4B	NM_001369145.1	c.2059-16T>C		intron_variant	Intron 19 of 19		NP_001356074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL4B	ENST00000371322.11	c.2593-16T>C		intron_variant	Intron 19 of 19	1	NM_001079872.2	ENSP00000360373.5
CUL4B	ENST00000681206.1	c.2707-16T>C		intron_variant	Intron 22 of 22			ENSP00000505480.1
CUL4B	ENST00000680673.1	c.2647-16T>C		intron_variant	Intron 21 of 21			ENSP00000505084.1
CUL4B	ENST00000681253.1	c.2647-16T>C		intron_variant	Intron 22 of 22			ENSP00000506259.1
CUL4B	ENST00000681652.1	c.2647-16T>C		intron_variant	Intron 24 of 24			ENSP00000505176.1
CUL4B	ENST00000336592.11	c.2608-16T>C		intron_variant	Intron 20 of 20	5		ENSP00000338919.6
CUL4B	ENST00000674137.11	c.2599-16T>C		intron_variant	Intron 19 of 19			ENSP00000501019.6
CUL4B	ENST00000681090.1	c.2500-16T>C		intron_variant	Intron 19 of 19			ENSP00000506288.1
CUL4B	ENST00000404115.8	c.2440-16T>C		intron_variant	Intron 18 of 18	1		ENSP00000384109.4
CUL4B	ENST00000679927.1	c.2248-16T>C		intron_variant	Intron 20 of 20			ENSP00000505603.1
CUL4B	ENST00000371323.3	c.2059-16T>C		intron_variant	Intron 19 of 19	5		ENSP00000360374.3
CUL4B	ENST00000680474.1	c.*39-16T>C		intron_variant	Intron 19 of 19			ENSP00000505562.1
CUL4B	ENST00000679844.1	c.1930-16T>C		intron_variant	Intron 17 of 17			ENSP00000505239.1
CUL4B	ENST00000673919.1	n.*2040-16T>C		intron_variant	Intron 20 of 20			ENSP00000500994.1
CUL4B	ENST00000674073.2	n.*149-16T>C		intron_variant	Intron 17 of 17			ENSP00000501262.2
CUL4B	ENST00000679405.1	n.*1802-16T>C		intron_variant	Intron 21 of 21			ENSP00000504985.1
CUL4B	ENST00000679432.1	n.*1802-16T>C		intron_variant	Intron 21 of 21			ENSP00000505343.1
CUL4B	ENST00000680918.1	n.*1509-16T>C		intron_variant	Intron 17 of 17			ENSP00000505955.1
CUL4B	ENST00000681080.1	n.*1802-16T>C		intron_variant	Intron 19 of 19			ENSP00000505898.1
CUL4B	ENST00000681189.1	n.*759-16T>C		intron_variant	Intron 19 of 19			ENSP00000505973.1
CUL4B	ENST00000681333.1	n.*3486-16T>C		intron_variant	Intron 16 of 16			ENSP00000505739.1
CUL4B	ENST00000681908.1	n.*765-16T>C		intron_variant	Intron 19 of 19			ENSP00000505777.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000857 AC: 8 AN: 933439 Hom.: 0 Cov.: 16 AF XY: 0.00000405 AC XY: 1 AN XY: 247171

African (AFR) AF: 0.00 AC: 0 AN: 23284

American (AMR) AF: 0.00 AC: 0 AN: 34448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17721

East Asian (EAS) AF: 0.00 AC: 0 AN: 28354

South Asian (SAS) AF: 0.00 AC: 0 AN: 50482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3705

European-Non Finnish (NFE) AF: 0.0000114 AC: 8 AN: 698838

Other (OTH) AF: 0.00 AC: 0 AN: 40101

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

X-linked intellectual disability Cabezas type Benign:1

Jul 19, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.69
PhyloP100		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1048730072; hg19: chrX-119660727;