chrX-120526754-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001079872.2(CUL4B):​c.*7G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000871 in 1,147,536 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.0000039 ( 0 hom. 1 hem. )

Consequence

CUL4B
NM_001079872.2 3_prime_UTR

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.02
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 -5 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant X-120526754-C-T is Benign according to our data. Variant chrX-120526754-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 388445.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CUL4BNM_001079872.2 linkc.*7G>A 3_prime_UTR_variant Exon 20 of 20 ENST00000371322.11 NP_001073341.1 Q13620-1
CUL4BNM_003588.4 linkc.*7G>A 3_prime_UTR_variant Exon 22 of 22 NP_003579.3 Q13620-2
CUL4BNM_001330624.2 linkc.*7G>A 3_prime_UTR_variant Exon 21 of 21 NP_001317553.1 K4DI93
CUL4BNM_001369145.1 linkc.*7G>A 3_prime_UTR_variant Exon 20 of 20 NP_001356074.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CUL4BENST00000371322 linkc.*7G>A 3_prime_UTR_variant Exon 20 of 20 1 NM_001079872.2 ENSP00000360373.5 Q13620-1
CUL4BENST00000681206 linkc.*7G>A 3_prime_UTR_variant Exon 23 of 23 ENSP00000505480.1 A0A7P0T954
CUL4BENST00000680673 linkc.*7G>A 3_prime_UTR_variant Exon 22 of 22 ENSP00000505084.1 Q13620-2
CUL4BENST00000681253 linkc.*7G>A 3_prime_UTR_variant Exon 23 of 23 ENSP00000506259.1 Q13620-2
CUL4BENST00000681652 linkc.*7G>A 3_prime_UTR_variant Exon 25 of 25 ENSP00000505176.1 Q13620-2
CUL4BENST00000336592 linkc.*7G>A 3_prime_UTR_variant Exon 21 of 21 5 ENSP00000338919.6 K4DI93
CUL4BENST00000674137 linkc.*7G>A 3_prime_UTR_variant Exon 20 of 20 ENSP00000501019.6 A0A669KAX4
CUL4BENST00000681090 linkc.*7G>A 3_prime_UTR_variant Exon 20 of 20 ENSP00000506288.1 A0A7P0TAQ3
CUL4BENST00000404115 linkc.*7G>A 3_prime_UTR_variant Exon 19 of 19 1 ENSP00000384109.4 A0A804CL36
CUL4BENST00000679927 linkc.*7G>A 3_prime_UTR_variant Exon 21 of 21 ENSP00000505603.1 A0A7P0T9L3
CUL4BENST00000371323 linkc.*7G>A 3_prime_UTR_variant Exon 20 of 20 5 ENSP00000360374.3 Q13620-3
CUL4BENST00000680474 linkc.*141G>A 3_prime_UTR_variant Exon 20 of 20 ENSP00000505562.1 A0A7P0T9C8
CUL4BENST00000679844 linkc.*7G>A 3_prime_UTR_variant Exon 18 of 18 ENSP00000505239.1 A0A7P0T8P8
CUL4BENST00000673919.1 linkn.*2142G>A non_coding_transcript_exon_variant Exon 21 of 21 ENSP00000500994.1 A0A669KAU9
CUL4BENST00000674073.2 linkn.*251G>A non_coding_transcript_exon_variant Exon 18 of 18 ENSP00000501262.2 A0A669KBG9
CUL4BENST00000679405.1 linkn.*1904G>A non_coding_transcript_exon_variant Exon 22 of 22 ENSP00000504985.1 A0A7P0Z439
CUL4BENST00000679432.1 linkn.*1904G>A non_coding_transcript_exon_variant Exon 22 of 22 ENSP00000505343.1 A0A7P0T8W4
CUL4BENST00000680918.1 linkn.*1611G>A non_coding_transcript_exon_variant Exon 18 of 18 ENSP00000505955.1 A0A7P0Z4G9
CUL4BENST00000681080.1 linkn.*1904G>A non_coding_transcript_exon_variant Exon 20 of 20 ENSP00000505898.1 A0A7P0Z4E4
CUL4BENST00000681189.1 linkn.*861G>A non_coding_transcript_exon_variant Exon 20 of 20 ENSP00000505973.1 A0A7P0TAF9
CUL4BENST00000681333.1 linkn.*3588G>A non_coding_transcript_exon_variant Exon 17 of 17 ENSP00000505739.1 A0A7P0T9R8
CUL4BENST00000681908.1 linkn.*867G>A non_coding_transcript_exon_variant Exon 20 of 20 ENSP00000505777.1 A0A7P0T9P5
CUL4BENST00000673919.1 linkn.*2142G>A 3_prime_UTR_variant Exon 21 of 21 ENSP00000500994.1 A0A669KAU9
CUL4BENST00000674073.2 linkn.*251G>A 3_prime_UTR_variant Exon 18 of 18 ENSP00000501262.2 A0A669KBG9
CUL4BENST00000679405.1 linkn.*1904G>A 3_prime_UTR_variant Exon 22 of 22 ENSP00000504985.1 A0A7P0Z439
CUL4BENST00000679432.1 linkn.*1904G>A 3_prime_UTR_variant Exon 22 of 22 ENSP00000505343.1 A0A7P0T8W4
CUL4BENST00000680918.1 linkn.*1611G>A 3_prime_UTR_variant Exon 18 of 18 ENSP00000505955.1 A0A7P0Z4G9
CUL4BENST00000681080.1 linkn.*1904G>A 3_prime_UTR_variant Exon 20 of 20 ENSP00000505898.1 A0A7P0Z4E4
CUL4BENST00000681189.1 linkn.*861G>A 3_prime_UTR_variant Exon 20 of 20 ENSP00000505973.1 A0A7P0TAF9
CUL4BENST00000681333.1 linkn.*3588G>A 3_prime_UTR_variant Exon 17 of 17 ENSP00000505739.1 A0A7P0T9R8
CUL4BENST00000681908.1 linkn.*867G>A 3_prime_UTR_variant Exon 20 of 20 ENSP00000505777.1 A0A7P0T9P5

Frequencies

GnomAD3 genomes
AF:
0.0000535
AC:
6
AN:
112073
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34249
show subpopulations
Gnomad AFR
AF:
0.000195
Gnomad AMI
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000109
AC:
2
AN:
183015
Hom.:
0
AF XY:
0.0000148
AC XY:
1
AN XY:
67561
show subpopulations
Gnomad AFR exome
AF:
0.000152
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000386
AC:
4
AN:
1035463
Hom.:
0
Cov.:
20
AF XY:
0.00000318
AC XY:
1
AN XY:
314813
show subpopulations
Gnomad4 AFR exome
AF:
0.000159
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000535
AC:
6
AN:
112073
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34249
show subpopulations
Gnomad4 AFR
AF:
0.000195
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 14, 2023
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Variant summary: CUL4B c.*7G>A is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 1.1e-05 in 183015 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.*7G>A in individuals affected with X-linked intellectual disability Cabezas type and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. -

not provided Benign:1
May 18, 2020
GeneDx
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
-0.47
CADD
Benign
13
DANN
Benign
0.79

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: rs769730471; hg19: chrX-119660609; API