NM_001079872.2:c.2593-207delA

Variant names:

• chrX-120527062-CT-C
• rs918835696
• NM_001079872.2:c.2593-207delA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001079872.2(CUL4B):​c.2593-207delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 100,720 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0020 (0 hom., 25 hem., cov: 21)
• Consequence: CUL4B NM_001079872.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• 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 -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 at 25 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL4B	NM_001079872.2	c.2593-207delA		intron_variant	Intron 19 of 19	ENST00000371322.11	NP_001073341.1
CUL4B	NM_003588.4	c.2647-207delA		intron_variant	Intron 21 of 21		NP_003579.3
CUL4B	NM_001330624.2	c.2608-207delA		intron_variant	Intron 20 of 20		NP_001317553.1
CUL4B	NM_001369145.1	c.2059-207delA		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.2593-207delA		intron_variant	Intron 19 of 19	1	NM_001079872.2	ENSP00000360373.5
CUL4B	ENST00000681206.1	c.2707-207delA		intron_variant	Intron 22 of 22			ENSP00000505480.1
CUL4B	ENST00000680673.1	c.2647-207delA		intron_variant	Intron 21 of 21			ENSP00000505084.1
CUL4B	ENST00000681253.1	c.2647-207delA		intron_variant	Intron 22 of 22			ENSP00000506259.1
CUL4B	ENST00000681652.1	c.2647-207delA		intron_variant	Intron 24 of 24			ENSP00000505176.1
CUL4B	ENST00000336592.11	c.2608-207delA		intron_variant	Intron 20 of 20	5		ENSP00000338919.6
CUL4B	ENST00000674137.11	c.2599-207delA		intron_variant	Intron 19 of 19			ENSP00000501019.6
CUL4B	ENST00000681090.1	c.2500-207delA		intron_variant	Intron 19 of 19			ENSP00000506288.1
CUL4B	ENST00000404115.8	c.2440-207delA		intron_variant	Intron 18 of 18	1		ENSP00000384109.4
CUL4B	ENST00000679927.1	c.2248-207delA		intron_variant	Intron 20 of 20			ENSP00000505603.1
CUL4B	ENST00000371323.3	c.2059-207delA		intron_variant	Intron 19 of 19	5		ENSP00000360374.3
CUL4B	ENST00000680474.1	c.*39-207delA		intron_variant	Intron 19 of 19			ENSP00000505562.1
CUL4B	ENST00000679844.1	c.1930-207delA		intron_variant	Intron 17 of 17			ENSP00000505239.1
CUL4B	ENST00000673919.1	n.*2040-207delA		intron_variant	Intron 20 of 20			ENSP00000500994.1
CUL4B	ENST00000674073.2	n.*149-207delA		intron_variant	Intron 17 of 17			ENSP00000501262.2
CUL4B	ENST00000679405.1	n.*1802-207delA		intron_variant	Intron 21 of 21			ENSP00000504985.1
CUL4B	ENST00000679432.1	n.*1802-207delA		intron_variant	Intron 21 of 21			ENSP00000505343.1
CUL4B	ENST00000680918.1	n.*1509-207delA		intron_variant	Intron 17 of 17			ENSP00000505955.1
CUL4B	ENST00000681080.1	n.*1802-207delA		intron_variant	Intron 19 of 19			ENSP00000505898.1
CUL4B	ENST00000681189.1	n.*759-207delA		intron_variant	Intron 19 of 19			ENSP00000505973.1
CUL4B	ENST00000681333.1	n.*3486-207delA		intron_variant	Intron 16 of 16			ENSP00000505739.1
CUL4B	ENST00000681908.1	n.*765-207delA		intron_variant	Intron 19 of 19			ENSP00000505777.1

Frequencies

GnomAD3 genomes AF: 0.00200 AC: 201 AN: 100722 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00406

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00193

Gnomad ASJ AF: 0.000409

Gnomad EAS AF: 0.000303

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00765

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000653

Gnomad OTH AF: 0.00303

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

GnomAD4 genome AF: 0.00202 AC: 203 AN: 100720 Hom.: 0 Cov.: 21 AF XY: 0.000903 AC XY: 25 AN XY: 27674

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00412 AC: 116 AN: 28137

American (AMR) AF: 0.00193 AC: 18 AN: 9335

Ashkenazi Jewish (ASJ) AF: 0.000409 AC: 1 AN: 2442

East Asian (EAS) AF: 0.000304 AC: 1 AN: 3290

South Asian (SAS) AF: 0.00 AC: 0 AN: 2341

European-Finnish (FIN) AF: 0.00765 AC: 31 AN: 4050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 194

European-Non Finnish (NFE) AF: 0.000653 AC: 32 AN: 48968

Other (OTH) AF: 0.00301 AC: 4 AN: 1331

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000251 Hom.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

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: rs918835696; hg19: chrX-119660917; COSMIC: COSV104414185;