ENST00000673919.1:n.*2142G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The ENST00000673919.1(CUL4B):n.*2142G>A variant causes a non coding transcript exon 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
ENST00000673919.1 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.02

Publications

0 publications found

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]

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

CUL4B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
CUL4B	NM_001079872.2 link	c.*7G>A	3_prime_UTR_variant	Exon 20 of 20	ENST00000371322.11	NP_001073341.1	Q13620-1
CUL4B	NM_003588.4 link	c.*7G>A	3_prime_UTR_variant	Exon 22 of 22		NP_003579.3	Q13620-2
CUL4B	NM_001330624.2 link	c.*7G>A	3_prime_UTR_variant	Exon 21 of 21		NP_001317553.1	K4DI93
CUL4B	NM_001369145.1 link	c.*7G>A	3_prime_UTR_variant	Exon 20 of 20		NP_001356074.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CUL4B	ENST00000673919.1 link	n.*2142G>A	non_coding_transcript_exon_variant	Exon 21 of 21			ENSP00000500994.1	A0A669KAU9
CUL4B	ENST00000674073.2 link	n.*251G>A	non_coding_transcript_exon_variant	Exon 18 of 18			ENSP00000501262.2	A0A669KBG9
CUL4B	ENST00000679405.1 link	n.*1904G>A	non_coding_transcript_exon_variant	Exon 22 of 22			ENSP00000504985.1	A0A7P0Z439
CUL4B	ENST00000679432.1 link	n.*1904G>A	non_coding_transcript_exon_variant	Exon 22 of 22			ENSP00000505343.1	A0A7P0T8W4
CUL4B	ENST00000680918.1 link	n.*1611G>A	non_coding_transcript_exon_variant	Exon 18 of 18			ENSP00000505955.1	A0A7P0Z4G9
CUL4B	ENST00000681080.1 link	n.*1904G>A	non_coding_transcript_exon_variant	Exon 20 of 20			ENSP00000505898.1	A0A7P0Z4E4
CUL4B	ENST00000681189.1 link	n.*861G>A	non_coding_transcript_exon_variant	Exon 20 of 20			ENSP00000505973.1	A0A7P0TAF9
CUL4B	ENST00000681333.1 link	n.*3588G>A	non_coding_transcript_exon_variant	Exon 17 of 17			ENSP00000505739.1	A0A7P0T9R8
CUL4B	ENST00000681908.1 link	n.*867G>A	non_coding_transcript_exon_variant	Exon 20 of 20			ENSP00000505777.1	A0A7P0T9P5
CUL4B	ENST00000371322.11 link	c.*7G>A	3_prime_UTR_variant	Exon 20 of 20	1	NM_001079872.2	ENSP00000360373.5	Q13620-1
CUL4B	ENST00000681206.1 link	c.*7G>A	3_prime_UTR_variant	Exon 23 of 23			ENSP00000505480.1	A0A7P0T954
CUL4B	ENST00000680673.1 link	c.*7G>A	3_prime_UTR_variant	Exon 22 of 22			ENSP00000505084.1	Q13620-2
CUL4B	ENST00000681253.1 link	c.*7G>A	3_prime_UTR_variant	Exon 23 of 23			ENSP00000506259.1	Q13620-2
CUL4B	ENST00000681652.1 link	c.*7G>A	3_prime_UTR_variant	Exon 25 of 25			ENSP00000505176.1	Q13620-2
CUL4B	ENST00000336592.11 link	c.*7G>A	3_prime_UTR_variant	Exon 21 of 21	5		ENSP00000338919.6	K4DI93
CUL4B	ENST00000674137.11 link	c.*7G>A	3_prime_UTR_variant	Exon 20 of 20			ENSP00000501019.6	A0A669KAX4
CUL4B	ENST00000681090.1 link	c.*7G>A	3_prime_UTR_variant	Exon 20 of 20			ENSP00000506288.1	A0A7P0TAQ3
CUL4B	ENST00000404115.8 link	c.*7G>A	3_prime_UTR_variant	Exon 19 of 19	1		ENSP00000384109.4	A0A804CL36
CUL4B	ENST00000679927.1 link	c.*7G>A	3_prime_UTR_variant	Exon 21 of 21			ENSP00000505603.1	A0A7P0T9L3
CUL4B	ENST00000371323.3 link	c.*7G>A	3_prime_UTR_variant	Exon 20 of 20	5		ENSP00000360374.3	Q13620-3
CUL4B	ENST00000680474.1 link	c.*141G>A	3_prime_UTR_variant	Exon 20 of 20			ENSP00000505562.1	A0A7P0T9C8
CUL4B	ENST00000679844.1 link	c.*7G>A	3_prime_UTR_variant	Exon 18 of 18			ENSP00000505239.1	A0A7P0T8P8
CUL4B	ENST00000673919.1 link	n.*2142G>A	3_prime_UTR_variant	Exon 21 of 21			ENSP00000500994.1	A0A669KAU9
CUL4B	ENST00000674073.2 link	n.*251G>A	3_prime_UTR_variant	Exon 18 of 18			ENSP00000501262.2	A0A669KBG9
CUL4B	ENST00000679405.1 link	n.*1904G>A	3_prime_UTR_variant	Exon 22 of 22			ENSP00000504985.1	A0A7P0Z439
CUL4B	ENST00000679432.1 link	n.*1904G>A	3_prime_UTR_variant	Exon 22 of 22			ENSP00000505343.1	A0A7P0T8W4
CUL4B	ENST00000680918.1 link	n.*1611G>A	3_prime_UTR_variant	Exon 18 of 18			ENSP00000505955.1	A0A7P0Z4G9
CUL4B	ENST00000681080.1 link	n.*1904G>A	3_prime_UTR_variant	Exon 20 of 20			ENSP00000505898.1	A0A7P0Z4E4
CUL4B	ENST00000681189.1 link	n.*861G>A	3_prime_UTR_variant	Exon 20 of 20			ENSP00000505973.1	A0A7P0TAF9
CUL4B	ENST00000681333.1 link	n.*3588G>A	3_prime_UTR_variant	Exon 17 of 17			ENSP00000505739.1	A0A7P0T9R8
CUL4B	ENST00000681908.1 link	n.*867G>A	3_prime_UTR_variant	Exon 20 of 20			ENSP00000505777.1	A0A7P0T9P5

Frequencies

GnomAD3 genomes

AF:

0.0000535

AC:

AN:

112073

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

183015

AF XY:

0.0000148

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000386

AC:

AN:

1035463

Hom.:

Cov.:

AF XY:

0.00000318

AC XY:

AN XY:

314813

show subpopulations

African (AFR)

AF:

0.000159

AC:

AN:

25182

American (AMR)

AF:

0.00

AC:

AN:

34659

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18484

East Asian (EAS)

AF:

0.00

AC:

AN:

28999

South Asian (SAS)

AF:

0.00

AC:

AN:

52648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38855

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3931

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

789150

Other (OTH)

AF:

0.00

AC:

AN:

43555

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000535

AC:

AN:

112073

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34249

show subpopulations

African (AFR)

AF:

0.000195

AC:

AN:

30824

American (AMR)

AF:

0.00

AC:

AN:

10552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3584

South Asian (SAS)

AF:

0.00

AC:

AN:

2751

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6077

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53210

Other (OTH)

AF:

0.00

AC:

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

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

(source)

DANN

Benign

0.79

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism

(source)

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

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ENST00000673919.1:n.*2142G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over