rs1260356990

Positions:

• chrX-120543779-G-A
• chrX-120543779-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2 PP3_Moderate BS2

The NM_001079872.2(CUL4B):​c.1204C>T​(p.Arg402Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000644 in 1,086,969 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000064 (0 hom. 2 hem.)
• Consequence: CUL4B NM_001079872.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.88

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CUL4B. . Gene score misZ 3.7714 (greater than the threshold 3.09). GenCC has associacion of gene with X-linked intellectual disability, Cabezas type.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.933
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUL4B	NM_001079872.2	c.1204C>T	p.Arg402Cys	missense_variant	8/20	ENST00000371322.11	NP_001073341.1
CUL4B	NM_003588.4	c.1258C>T	p.Arg420Cys	missense_variant	10/22		NP_003579.3
CUL4B	NM_001330624.2	c.1219C>T	p.Arg407Cys	missense_variant	9/21		NP_001317553.1
CUL4B	NM_001369145.1	c.670C>T	p.Arg224Cys	missense_variant	8/20		NP_001356074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL4B	ENST00000371322.11	c.1204C>T	p.Arg402Cys	missense_variant	8/20	1	NM_001079872.2	ENSP00000360373.5
CUL4B	ENST00000681206.1	c.1318C>T	p.Arg440Cys	missense_variant	11/23			ENSP00000505480.1
CUL4B	ENST00000680673.1	c.1258C>T	p.Arg420Cys	missense_variant	10/22			ENSP00000505084.1
CUL4B	ENST00000681253.1	c.1258C>T	p.Arg420Cys	missense_variant	11/23			ENSP00000506259.1
CUL4B	ENST00000681652.1	c.1258C>T	p.Arg420Cys	missense_variant	13/25			ENSP00000505176.1
CUL4B	ENST00000336592.11	c.1219C>T	p.Arg407Cys	missense_variant	9/21	5		ENSP00000338919.6
CUL4B	ENST00000674137.11	c.1204C>T	p.Arg402Cys	missense_variant	8/20			ENSP00000501019.6
CUL4B	ENST00000681090.1	c.1111C>T	p.Arg371Cys	missense_variant	8/20			ENSP00000506288.1
CUL4B	ENST00000404115.8	c.1204C>T	p.Arg402Cys	missense_variant	8/19	1		ENSP00000384109.4
CUL4B	ENST00000679927.1	c.859C>T	p.Arg287Cys	missense_variant	9/21			ENSP00000505603.1
CUL4B	ENST00000371323.3	c.670C>T	p.Arg224Cys	missense_variant	8/20	5		ENSP00000360374.3
CUL4B	ENST00000680474.1	c.646C>T	p.Arg216Cys	missense_variant	7/20			ENSP00000505562.1
CUL4B	ENST00000679844.1	c.646C>T	p.Arg216Cys	missense_variant	7/18			ENSP00000505239.1
CUL4B	ENST00000673919.1	n.*651C>T		non_coding_transcript_exon_variant	9/21			ENSP00000500994.1
CUL4B	ENST00000674073.2	n.646C>T		non_coding_transcript_exon_variant	7/18			ENSP00000501262.2
CUL4B	ENST00000679405.1	n.*413C>T		non_coding_transcript_exon_variant	10/22			ENSP00000504985.1
CUL4B	ENST00000679432.1	n.*413C>T		non_coding_transcript_exon_variant	10/22			ENSP00000505343.1
CUL4B	ENST00000680918.1	n.*120C>T		non_coding_transcript_exon_variant	6/18			ENSP00000505955.1
CUL4B	ENST00000681080.1	n.*413C>T		non_coding_transcript_exon_variant	8/20			ENSP00000505898.1
CUL4B	ENST00000681189.1	n.646C>T		non_coding_transcript_exon_variant	7/20			ENSP00000505973.1
CUL4B	ENST00000681333.1	n.*153C>T		non_coding_transcript_exon_variant	8/17			ENSP00000505739.1
CUL4B	ENST00000681869.1	n.646C>T		non_coding_transcript_exon_variant	7/17			ENSP00000505597.1
CUL4B	ENST00000681908.1	n.646C>T		non_coding_transcript_exon_variant	7/20			ENSP00000505777.1
CUL4B	ENST00000673919.1	n.*651C>T		3_prime_UTR_variant	9/21			ENSP00000500994.1
CUL4B	ENST00000679405.1	n.*413C>T		3_prime_UTR_variant	10/22			ENSP00000504985.1
CUL4B	ENST00000679432.1	n.*413C>T		3_prime_UTR_variant	10/22			ENSP00000505343.1
CUL4B	ENST00000680918.1	n.*120C>T		3_prime_UTR_variant	6/18			ENSP00000505955.1
CUL4B	ENST00000681080.1	n.*413C>T		3_prime_UTR_variant	8/20			ENSP00000505898.1
CUL4B	ENST00000681333.1	n.*153C>T		3_prime_UTR_variant	8/17			ENSP00000505739.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000644 AC: 7 AN: 1086969 Hom.: 0 Cov.: 28 AF XY: 0.00000566 AC XY: 2 AN XY: 353195

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: 0.00000721

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.58	.;.;D;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Pathogenic	0.82	D
MetaRNN	Pathogenic	0.93	D;D;D;D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	1.6	.;.;L;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-7.4	D;D;D;D
REVEL	Pathogenic	0.83
Sift	Benign	0.032	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;.
Polyphen		1.0	D;.;D;.
Vest4		0.71
MutPred		0.73		.;.;Gain of methylation at K419 (P = 0.0145);.;
MVP		0.99
MPC		1.9
ClinPred		1.0	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.92
gMVP		0.95

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

Publications

LitVar

Other links and lift over

dbSNP: rs1260356990; hg19: chrX-119677634;