X-120526872-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.12
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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
CUL4BNM_001079872.2 linkc.2593-16T>C intron_variant Intron 19 of 19 ENST00000371322.11 NP_001073341.1 Q13620-1
CUL4BNM_003588.4 linkc.2647-16T>C intron_variant Intron 21 of 21 NP_003579.3 Q13620-2
CUL4BNM_001330624.2 linkc.2608-16T>C intron_variant Intron 20 of 20 NP_001317553.1 K4DI93
CUL4BNM_001369145.1 linkc.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
CUL4BENST00000371322.11 linkc.2593-16T>C intron_variant Intron 19 of 19 1 NM_001079872.2 ENSP00000360373.5 Q13620-1
CUL4BENST00000681206.1 linkc.2707-16T>C intron_variant Intron 22 of 22 ENSP00000505480.1 A0A7P0T954
CUL4BENST00000680673.1 linkc.2647-16T>C intron_variant Intron 21 of 21 ENSP00000505084.1 Q13620-2
CUL4BENST00000681253.1 linkc.2647-16T>C intron_variant Intron 22 of 22 ENSP00000506259.1 Q13620-2
CUL4BENST00000681652.1 linkc.2647-16T>C intron_variant Intron 24 of 24 ENSP00000505176.1 Q13620-2
CUL4BENST00000336592.11 linkc.2608-16T>C intron_variant Intron 20 of 20 5 ENSP00000338919.6 K4DI93
CUL4BENST00000674137.11 linkc.2599-16T>C intron_variant Intron 19 of 19 ENSP00000501019.6 A0A669KAX4
CUL4BENST00000681090.1 linkc.2500-16T>C intron_variant Intron 19 of 19 ENSP00000506288.1 A0A7P0TAQ3
CUL4BENST00000404115.8 linkc.2440-16T>C intron_variant Intron 18 of 18 1 ENSP00000384109.4 A0A804CL36
CUL4BENST00000679927.1 linkc.2248-16T>C intron_variant Intron 20 of 20 ENSP00000505603.1 A0A7P0T9L3
CUL4BENST00000371323.3 linkc.2059-16T>C intron_variant Intron 19 of 19 5 ENSP00000360374.3 Q13620-3
CUL4BENST00000680474.1 linkc.*39-16T>C intron_variant Intron 19 of 19 ENSP00000505562.1 A0A7P0T9C8
CUL4BENST00000679844.1 linkc.1930-16T>C intron_variant Intron 17 of 17 ENSP00000505239.1 A0A7P0T8P8
CUL4BENST00000673919.1 linkn.*2040-16T>C intron_variant Intron 20 of 20 ENSP00000500994.1 A0A669KAU9
CUL4BENST00000674073.2 linkn.*149-16T>C intron_variant Intron 17 of 17 ENSP00000501262.2 A0A669KBG9
CUL4BENST00000679405.1 linkn.*1802-16T>C intron_variant Intron 21 of 21 ENSP00000504985.1 A0A7P0Z439
CUL4BENST00000679432.1 linkn.*1802-16T>C intron_variant Intron 21 of 21 ENSP00000505343.1 A0A7P0T8W4
CUL4BENST00000680918.1 linkn.*1509-16T>C intron_variant Intron 17 of 17 ENSP00000505955.1 A0A7P0Z4G9
CUL4BENST00000681080.1 linkn.*1802-16T>C intron_variant Intron 19 of 19 ENSP00000505898.1 A0A7P0Z4E4
CUL4BENST00000681189.1 linkn.*759-16T>C intron_variant Intron 19 of 19 ENSP00000505973.1 A0A7P0TAF9
CUL4BENST00000681333.1 linkn.*3486-16T>C intron_variant Intron 16 of 16 ENSP00000505739.1 A0A7P0T9R8
CUL4BENST00000681908.1 linkn.*765-16T>C intron_variant Intron 19 of 19 ENSP00000505777.1 A0A7P0T9P5

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
show subpopulations
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:
0.0000114
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

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
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1048730072; hg19: chrX-119660727; API