rs12393998

Variant names:

• chrX-120566227-A-C
• rs12393998
• ENST00000680673.1:c.68-5602T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000680673.1(CUL4B):​c.68-5602T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (7447 hom., 10567 hem., cov: 18)
• Consequence: CUL4B ENST00000680673.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 1 publications found

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

ENSG00000302007 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL4B	NM_003588.4	c.68-5602T>G		intron_variant	Intron 2 of 21		NP_003579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL4B	ENST00000680673.1	c.68-5602T>G		intron_variant	Intron 2 of 21			ENSP00000505084.1
CUL4B	ENST00000681253.1	c.68-5602T>G		intron_variant	Intron 3 of 22			ENSP00000506259.1
CUL4B	ENST00000681652.1	c.68-5602T>G		intron_variant	Intron 5 of 24			ENSP00000505176.1
ENSG00000302007	ENST00000783301.1	n.79+5343A>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 42604 AN: 103450 Hom.: 7445 Cov.: 18

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.412 AC: 42640 AN: 103477 Hom.: 7447 Cov.: 18 AF XY: 0.399 AC XY: 10567 AN XY: 26459

African (AFR) AF: 0.633 AC: 17927 AN: 28322

American (AMR) AF: 0.444 AC: 4138 AN: 9323

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 935 AN: 2557

East Asian (EAS) AF: 0.337 AC: 1074 AN: 3186

South Asian (SAS) AF: 0.293 AC: 656 AN: 2239

European-Finnish (FIN) AF: 0.284 AC: 1316 AN: 4627

Middle Eastern (MID) AF: 0.363 AC: 73 AN: 201

European-Non Finnish (NFE) AF: 0.309 AC: 15780 AN: 50997

Other (OTH) AF: 0.408 AC: 566 AN: 1386

Alfa AF: 0.360 Hom.: 43173

Bravo AF: 0.439

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.13
DANN	Benign	0.63
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12393998; hg19: chrX-119700082;