Genetic Variant CUL4B:c.2592+159dupA (chrX-120529942-G-GT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001079872.2(CUL4B):c.2592+159dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.53 ( 11815 hom., 14733 hem., cov: 0)

Consequence

CUL4B
NM_001079872.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.328

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: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet

CUL4B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant X-120529942-G-GT is Benign according to our data. Variant chrX-120529942-G-GT is described in ClinVar as Benign. ClinVar VariationId is 1231177.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079872.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CUL4B	NM_001079872.2	MANE Select	c.2592+159dupA	intron	N/A	NP_001073341.1	Q13620-1
CUL4B	NM_003588.4		c.2646+159dupA	intron	N/A	NP_003579.3
CUL4B	NM_001330624.2		c.2607+159dupA	intron	N/A	NP_001317553.1	K4DI93

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CUL4B	ENST00000371322.11	TSL:1 MANE Select	c.2592+159_2592+160insA	intron	N/A	ENSP00000360373.5	Q13620-1
CUL4B	ENST00000681206.1		c.2706+159_2706+160insA	intron	N/A	ENSP00000505480.1	A0A7P0T954
CUL4B	ENST00000680673.1		c.2646+159_2646+160insA	intron	N/A	ENSP00000505084.1	Q13620-2

Frequencies

GnomAD3 genomes

AF:

0.530

AC:

55382

AN:

104559

Hom.:

11822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.727

Gnomad AMR

AF:

0.689

Gnomad ASJ

AF:

0.647

Gnomad EAS

AF:

0.583

Gnomad SAS

AF:

0.595

Gnomad FIN

AF:

0.546

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.640

Gnomad OTH

AF:

0.552

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.529

AC:

55365

AN:

104569

Hom.:

11815

Cov.:

AF XY:

0.523

AC XY:

14733

AN XY:

28145

show subpopulations

African (AFR)

AF:

0.251

AC:

7271

AN:

28937

American (AMR)

AF:

0.690

AC:

6632

AN:

9613

Ashkenazi Jewish (ASJ)

AF:

0.647

AC:

1652

AN:

2554

East Asian (EAS)

AF:

0.583

AC:

1946

AN:

3339

South Asian (SAS)

AF:

0.593

AC:

1416

AN:

2389

European-Finnish (FIN)

AF:

0.546

AC:

2439

AN:

4466

Middle Eastern (MID)

AF:

0.552

AC:

112

AN:

203

European-Non Finnish (NFE)

AF:

0.640

AC:

32637

AN:

50997

Other (OTH)

AF:

0.552

AC:

777

AN:

1407

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

844

1688

2532

3376

4220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.374

Hom.:

1659

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.33

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

X-120529942-GTTT-GTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over