chrX-120526797-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001079872.2(CUL4B):ā€‹c.2652T>Cā€‹(p.Asp884Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,196,164 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.000036 ( 0 hom., 1 hem., cov: 23)
Exomes š‘“: 0.0000092 ( 0 hom. 3 hem. )

Consequence

CUL4B
NM_001079872.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.58
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant X-120526797-A-G is Benign according to our data. Variant chrX-120526797-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1794991.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.59 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CUL4BNM_001079872.2 linkc.2652T>C p.Asp884Asp synonymous_variant Exon 20 of 20 ENST00000371322.11 NP_001073341.1 Q13620-1
CUL4BNM_003588.4 linkc.2706T>C p.Asp902Asp synonymous_variant Exon 22 of 22 NP_003579.3 Q13620-2
CUL4BNM_001330624.2 linkc.2667T>C p.Asp889Asp synonymous_variant Exon 21 of 21 NP_001317553.1 K4DI93
CUL4BNM_001369145.1 linkc.2118T>C p.Asp706Asp synonymous_variant Exon 20 of 20 NP_001356074.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CUL4BENST00000371322.11 linkc.2652T>C p.Asp884Asp synonymous_variant Exon 20 of 20 1 NM_001079872.2 ENSP00000360373.5 Q13620-1
CUL4BENST00000681206.1 linkc.2766T>C p.Asp922Asp synonymous_variant Exon 23 of 23 ENSP00000505480.1 A0A7P0T954
CUL4BENST00000680673.1 linkc.2706T>C p.Asp902Asp synonymous_variant Exon 22 of 22 ENSP00000505084.1 Q13620-2
CUL4BENST00000681253.1 linkc.2706T>C p.Asp902Asp synonymous_variant Exon 23 of 23 ENSP00000506259.1 Q13620-2
CUL4BENST00000681652.1 linkc.2706T>C p.Asp902Asp synonymous_variant Exon 25 of 25 ENSP00000505176.1 Q13620-2
CUL4BENST00000336592.11 linkc.2667T>C p.Asp889Asp synonymous_variant Exon 21 of 21 5 ENSP00000338919.6 K4DI93
CUL4BENST00000674137.11 linkc.2658T>C p.Asp886Asp synonymous_variant Exon 20 of 20 ENSP00000501019.6 A0A669KAX4
CUL4BENST00000681090.1 linkc.2559T>C p.Asp853Asp synonymous_variant Exon 20 of 20 ENSP00000506288.1 A0A7P0TAQ3
CUL4BENST00000404115.8 linkc.2499T>C p.Asp833Asp synonymous_variant Exon 19 of 19 1 ENSP00000384109.4 A0A804CL36
CUL4BENST00000679927.1 linkc.2307T>C p.Asp769Asp synonymous_variant Exon 21 of 21 ENSP00000505603.1 A0A7P0T9L3
CUL4BENST00000371323.3 linkc.2118T>C p.Asp706Asp synonymous_variant Exon 20 of 20 5 ENSP00000360374.3 Q13620-3
CUL4BENST00000679844.1 linkc.1989T>C p.Asp663Asp synonymous_variant Exon 18 of 18 ENSP00000505239.1 A0A7P0T8P8
CUL4BENST00000680474 linkc.*98T>C 3_prime_UTR_variant Exon 20 of 20 ENSP00000505562.1 A0A7P0T9C8
CUL4BENST00000673919.1 linkn.*2099T>C non_coding_transcript_exon_variant Exon 21 of 21 ENSP00000500994.1 A0A669KAU9
CUL4BENST00000674073.2 linkn.*208T>C non_coding_transcript_exon_variant Exon 18 of 18 ENSP00000501262.2 A0A669KBG9
CUL4BENST00000679405.1 linkn.*1861T>C non_coding_transcript_exon_variant Exon 22 of 22 ENSP00000504985.1 A0A7P0Z439
CUL4BENST00000679432.1 linkn.*1861T>C non_coding_transcript_exon_variant Exon 22 of 22 ENSP00000505343.1 A0A7P0T8W4
CUL4BENST00000680918.1 linkn.*1568T>C non_coding_transcript_exon_variant Exon 18 of 18 ENSP00000505955.1 A0A7P0Z4G9
CUL4BENST00000681080.1 linkn.*1861T>C non_coding_transcript_exon_variant Exon 20 of 20 ENSP00000505898.1 A0A7P0Z4E4
CUL4BENST00000681189.1 linkn.*818T>C non_coding_transcript_exon_variant Exon 20 of 20 ENSP00000505973.1 A0A7P0TAF9
CUL4BENST00000681333.1 linkn.*3545T>C non_coding_transcript_exon_variant Exon 17 of 17 ENSP00000505739.1 A0A7P0T9R8
CUL4BENST00000681908.1 linkn.*824T>C non_coding_transcript_exon_variant Exon 20 of 20 ENSP00000505777.1 A0A7P0T9P5
CUL4BENST00000673919.1 linkn.*2099T>C 3_prime_UTR_variant Exon 21 of 21 ENSP00000500994.1 A0A669KAU9
CUL4BENST00000674073.2 linkn.*208T>C 3_prime_UTR_variant Exon 18 of 18 ENSP00000501262.2 A0A669KBG9
CUL4BENST00000679405.1 linkn.*1861T>C 3_prime_UTR_variant Exon 22 of 22 ENSP00000504985.1 A0A7P0Z439
CUL4BENST00000679432.1 linkn.*1861T>C 3_prime_UTR_variant Exon 22 of 22 ENSP00000505343.1 A0A7P0T8W4
CUL4BENST00000680918.1 linkn.*1568T>C 3_prime_UTR_variant Exon 18 of 18 ENSP00000505955.1 A0A7P0Z4G9
CUL4BENST00000681080.1 linkn.*1861T>C 3_prime_UTR_variant Exon 20 of 20 ENSP00000505898.1 A0A7P0Z4E4
CUL4BENST00000681189.1 linkn.*818T>C 3_prime_UTR_variant Exon 20 of 20 ENSP00000505973.1 A0A7P0TAF9
CUL4BENST00000681333.1 linkn.*3545T>C 3_prime_UTR_variant Exon 17 of 17 ENSP00000505739.1 A0A7P0T9R8
CUL4BENST00000681908.1 linkn.*824T>C 3_prime_UTR_variant Exon 20 of 20 ENSP00000505777.1 A0A7P0T9P5

Frequencies

GnomAD3 genomes
AF:
0.0000357
AC:
4
AN:
112131
Hom.:
0
Cov.:
23
AF XY:
0.0000292
AC XY:
1
AN XY:
34261
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00294
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000376
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000219
AC:
4
AN:
183050
Hom.:
0
AF XY:
0.0000296
AC XY:
2
AN XY:
67578
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000489
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000922
AC:
10
AN:
1084033
Hom.:
0
Cov.:
26
AF XY:
0.00000854
AC XY:
3
AN XY:
351195
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:
0.0000108
Gnomad4 OTH exome
AF:
0.0000220
GnomAD4 genome
AF:
0.0000357
AC:
4
AN:
112131
Hom.:
0
Cov.:
23
AF XY:
0.0000292
AC XY:
1
AN XY:
34261
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000376
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000868
Hom.:
1
Bravo
AF:
0.0000491
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
Jul 30, 2020
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

CUL4B-related disorder Benign:1
Feb 17, 2022
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

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

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
CADD
Benign
6.6
DANN
Benign
0.53

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: rs768424127; hg19: chrX-119660652; API