X-120527062-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001079872.2(CUL4B):c.2593-207_2593-206insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 100,788 control chromosomes in the GnomAD database, including 40 homozygotes. There are 468 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.023 (40 hom., 468 hem., cov: 21)
• Consequence: CUL4B NM_001079872.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.17

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-120527062-C-CT is Benign according to our data. Variant chrX-120527062-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 1213151.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0227 (2285/100788) while in subpopulation NFE AF= 0.0348 (1705/48980). AF 95% confidence interval is 0.0334. There are 40 homozygotes in gnomad4. There are 468 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 40 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUL4B	NM_001079872.2	c.2593-207_2593-206insA		intron_variant		ENST00000371322.11
CUL4B	NM_001330624.2	c.2608-207_2608-206insA		intron_variant
CUL4B	NM_001369145.1	c.2059-207_2059-206insA		intron_variant
CUL4B	NM_003588.4	c.2647-207_2647-206insA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUL4B	ENST00000371322.11	c.2593-207_2593-206insA		intron_variant		1	NM_001079872.2

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 2285 AN: 100793 Hom.: 40 Cov.: 21 AF XY: 0.0169 AC XY: 468 AN XY: 27679

Gnomad AFR AF: 0.00619

Gnomad AMI AF: 0.0111

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.0217

Gnomad EAS AF: 0.00939

Gnomad SAS AF: 0.0144

Gnomad FIN AF: 0.0283

Gnomad MID AF: 0.0425

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.0167

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

GnomAD4 genome AF: 0.0227 AC: 2285 AN: 100788 Hom.: 40 Cov.: 21 AF XY: 0.0169 AC XY: 468 AN XY: 27682

Gnomad4 AFR AF: 0.00618

Gnomad4 AMR AF: 0.0145

Gnomad4 ASJ AF: 0.0217

Gnomad4 EAS AF: 0.00943

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.0283

Gnomad4 NFE AF: 0.0348

Gnomad4 OTH AF: 0.0165

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs918835696; hg19: chrX-119660917;