NM_001079872.2:c.847-10delT

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001079872.2(CUL4B):c.847-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,096,758 control chromosomes in the GnomAD database, including 6 homozygotes. There are 268 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 2 hom., 135 hem., cov: 22)

Exomes 𝑓: 0.00062 ( 4 hom. 133 hem. )

Consequence

CUL4B
NM_001079872.2 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.333

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 -16 ACMG points.

BP6

Variant X-120545526-GA-G is Benign according to our data. Variant chrX-120545526-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 418559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-120545526-GA-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00479 (520/108534) while in subpopulation AFR AF= 0.0163 (488/29872). AF 95% confidence interval is 0.0151. There are 2 homozygotes in gnomad4. There are 135 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CUL4B	NM_001079872.2 link	c.847-10delT	intron_variant	Intron 4 of 19	ENST00000371322.11	NP_001073341.1	Q13620-1
CUL4B	NM_003588.4 link	c.901-10delT	intron_variant	Intron 6 of 21		NP_003579.3	Q13620-2
CUL4B	NM_001330624.2 link	c.862-10delT	intron_variant	Intron 5 of 20		NP_001317553.1	K4DI93
CUL4B	NM_001369145.1 link	c.313-10delT	intron_variant	Intron 4 of 19		NP_001356074.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CUL4B	ENST00000371322.11 link	c.847-10delT	intron_variant	Intron 4 of 19	1	NM_001079872.2	ENSP00000360373.5	Q13620-1
CUL4B	ENST00000681206.1 link	c.961-10delT	intron_variant	Intron 7 of 22			ENSP00000505480.1	A0A7P0T954
CUL4B	ENST00000680673.1 link	c.901-10delT	intron_variant	Intron 6 of 21			ENSP00000505084.1	Q13620-2
CUL4B	ENST00000681253.1 link	c.901-10delT	intron_variant	Intron 7 of 22			ENSP00000506259.1	Q13620-2
CUL4B	ENST00000681652.1 link	c.901-10delT	intron_variant	Intron 9 of 24			ENSP00000505176.1	Q13620-2
CUL4B	ENST00000336592.11 link	c.862-10delT	intron_variant	Intron 5 of 20	5		ENSP00000338919.6	K4DI93
CUL4B	ENST00000674137.11 link	c.847-10delT	intron_variant	Intron 4 of 19			ENSP00000501019.6	A0A669KAX4
CUL4B	ENST00000681090.1 link	c.847-10delT	intron_variant	Intron 4 of 19			ENSP00000506288.1	A0A7P0TAQ3
CUL4B	ENST00000404115.8 link	c.847-10delT	intron_variant	Intron 4 of 18	1		ENSP00000384109.4	A0A804CL36
CUL4B	ENST00000679927.1 link	c.502-10delT	intron_variant	Intron 5 of 20			ENSP00000505603.1	A0A7P0T9L3
CUL4B	ENST00000371323.3 link	c.313-10delT	intron_variant	Intron 4 of 19	5		ENSP00000360374.3	Q13620-3
CUL4B	ENST00000680474.1 link	c.289-10delT	intron_variant	Intron 3 of 19			ENSP00000505562.1	A0A7P0T9C8
CUL4B	ENST00000679844.1 link	c.289-10delT	intron_variant	Intron 3 of 17			ENSP00000505239.1	A0A7P0T8P8
CUL4B	ENST00000673919.1 link	n.*294-10delT	intron_variant	Intron 5 of 20			ENSP00000500994.1	A0A669KAU9
CUL4B	ENST00000674073.2 link	n.289-10delT	intron_variant	Intron 3 of 17			ENSP00000501262.2	A0A669KBG9
CUL4B	ENST00000679405.1 link	n.*56-10delT	intron_variant	Intron 6 of 21			ENSP00000504985.1	A0A7P0Z439
CUL4B	ENST00000679432.1 link	n.*56-10delT	intron_variant	Intron 6 of 21			ENSP00000505343.1	A0A7P0T8W4
CUL4B	ENST00000680918.1 link	n.289-10delT	intron_variant	Intron 3 of 17			ENSP00000505955.1	A0A7P0Z4G9
CUL4B	ENST00000681080.1 link	n.*56-10delT	intron_variant	Intron 4 of 19			ENSP00000505898.1	A0A7P0Z4E4
CUL4B	ENST00000681189.1 link	n.289-10delT	intron_variant	Intron 3 of 19			ENSP00000505973.1	A0A7P0TAF9
CUL4B	ENST00000681333.1 link	n.847-10delT	intron_variant	Intron 4 of 16			ENSP00000505739.1	A0A7P0T9R8
CUL4B	ENST00000681869.1 link	n.289-10delT	intron_variant	Intron 3 of 16			ENSP00000505597.1	A0A7P0T9D0
CUL4B	ENST00000681908.1 link	n.289-10delT	intron_variant	Intron 3 of 19			ENSP00000505777.1	A0A7P0T9P5

Frequencies

GnomAD3 genomes

AF:

0.00476

AC:

516

AN:

108490

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

131

AN XY:

31510

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00256

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:

0.00413

GnomAD3 exomes

AF:

0.00146

AC:

165

AN:

112836

Hom.:

AF XY:

0.00109

AC XY:

AN XY:

34842

show subpopulations

Gnomad AFR exome

AF:

0.0182

Gnomad AMR exome

AF:

0.000718

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000789

Gnomad FIN exome

AF:

0.000325

Gnomad NFE exome

AF:

0.000179

Gnomad OTH exome

AF:

0.000989

GnomAD4 exome

AF:

0.000622

AC:

615

AN:

988224

Hom.:

Cov.:

AF XY:

0.000463

AC XY:

133

AN XY:

286982

show subpopulations

Gnomad4 AFR exome

AF:

0.0175

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000355

Gnomad4 SAS exome

AF:

0.0000626

Gnomad4 FIN exome

AF:

0.0000796

Gnomad4 NFE exome

AF:

0.0000976

Gnomad4 OTH exome

AF:

0.00176

GnomAD4 genome

AF:

0.00479

AC:

520

AN:

108534

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

135

AN XY:

31566

show subpopulations

Gnomad4 AFR

AF:

0.0163

Gnomad4 AMR

AF:

0.00255

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:

0.00409

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.00546

Asia WGS

AF:

0.00239

AC:

AN:

2518

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

X-linked intellectual disability Cabezas type

Benign:3

Dec 19, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 08, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 17, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Nov 01, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Inborn genetic diseases

Benign:1

Sep 16, 2014

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Jan 16, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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