Variant X-120560261-TGAGGAGGAG-TGAGGAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2

The NM_001079872.2(CUL4B):c.375_377del(p.Ser128del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000816 in 1,176,913 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000085 ( 0 hom. 12 hem. )

Consequence

CUL4B
NM_001079872.2 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.25

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001079872.2

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CUL4B	NM_001079872.2 linkuse as main transcript	c.375_377del	p.Ser128del	inframe_deletion	1/20	ENST00000371322.11
CUL4B	NM_001330624.2 linkuse as main transcript	c.390_392del	p.Ser133del	inframe_deletion	2/21
CUL4B	NM_003588.4 linkuse as main transcript	c.429_431del	p.Ser146del	inframe_deletion	3/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUL4B	ENST00000371322.11 linkuse as main transcript	c.375_377del	p.Ser128del	inframe_deletion	1/20	1	NM_001079872.2		Q13620-1

Frequencies

GnomAD3 genomes

AF:

0.0000451

AC:

AN:

110981

Hom.:

Cov.:

AF XY:

0.0000600

AC XY:

AN XY:

33321

show subpopulations

Gnomad AFR

AF:

0.0000655

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000959

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:

0.0000378

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000520

AC:

AN:

173145

Hom.:

AF XY:

0.0000162

AC XY:

AN XY:

61627

show subpopulations

Gnomad AFR exome

AF:

0.0000795

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:

0.000340

Gnomad NFE exome

AF:

0.0000385

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000854

AC:

AN:

1065932

Hom.:

AF XY:

0.0000345

AC XY:

AN XY:

347582

show subpopulations

Gnomad4 AFR exome

AF:

0.0000777

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000340

Gnomad4 SAS exome

AF:

0.0000769

Gnomad4 FIN exome

AF:

0.0000761

Gnomad4 NFE exome

AF:

0.0000930

Gnomad4 OTH exome

AF:

0.000112

GnomAD4 genome

AF:

0.0000451

AC:

AN:

110981

Hom.:

Cov.:

AF XY:

0.0000600

AC XY:

AN XY:

33321

show subpopulations

Gnomad4 AFR

AF:

0.0000655

Gnomad4 AMR

AF:

0.0000959

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000378

Gnomad4 OTH

AF:

0.00

Asia WGS

AF:

0.00438

AC:

AN:

2522

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

X-linked intellectual disability Cabezas type

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 06, 2022

- -

CUL4B-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 16, 2021

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). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over