Variant rs145134351 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_ModerateBP6_ModerateBS2

The NM_001079872.2(CUL4B):c.139A>G(p.Ser47Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000281 in 1,208,975 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000026 ( 0 hom. 9 hem. )

Consequence

CUL4B
NM_001079872.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.26

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CUL4B. . Gene score misZ 3.7714 (greater than the threshold 3.09). GenCC has associacion of gene with X-linked intellectual disability, Cabezas type.

BP4

Computational evidence support a benign effect (MetaRNN=0.24711385).

BP6

Variant X-120560500-T-C is Benign according to our data. Variant chrX-120560500-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 572136.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CUL4B	NM_001079872.2 linkuse as main transcript	c.139A>G	p.Ser47Gly	missense_variant	1/20	ENST00000371322.11
CUL4B	NM_003588.4 linkuse as main transcript	c.193A>G	p.Ser65Gly	missense_variant	3/22
CUL4B	NM_001330624.2 linkuse as main transcript	c.154A>G	p.Ser52Gly	missense_variant	2/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUL4B	ENST00000371322.11 linkuse as main transcript	c.139A>G	p.Ser47Gly	missense_variant	1/20	1	NM_001079872.2		Q13620-1

Frequencies

GnomAD3 genomes

AF:

0.0000448

AC:

AN:

111557

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33717

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000941

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

181916

Hom.:

AF XY:

0.0000301

AC XY:

AN XY:

66450

show subpopulations

Gnomad AFR exome

AF:

0.0000766

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:

0.0000247

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000264

AC:

AN:

1097418

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

362782

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000321

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000448

AC:

AN:

111557

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33717

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:

0.0000941

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

X-linked intellectual disability Cabezas type

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.082

.;.;T

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.61

T;T;T

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.0

.;.;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.37

N;N;N

REVEL

Benign

0.20

Sift

Uncertain

0.0070

D;D;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.95

P;.;P

Vest4

0.28

MVP

0.85

MPC

0.71

ClinPred

0.18

GERP RS

5.4

Varity_R

0.18

gMVP

0.21

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