rs12393998

chrX-120566227-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003588.4(CUL4B):c.68-5602T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 103,477 control chromosomes in the GnomAD database, including 7,447 homozygotes. There are 10,567 hemizygotes in GnomAD. 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 NM_003588.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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 -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/exons	MANE	UniProt
CUL4B	NM_003588.4	c.68-5602T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUL4B	ENST00000680673.1	c.68-5602T>G		intron_variant
CUL4B	ENST00000681253.1	c.68-5602T>G		intron_variant
CUL4B	ENST00000681652.1	c.68-5602T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.412 AC: 42604 AN: 103450 Hom.: 7445 Cov.: 18 AF XY: 0.399 AC XY: 10532 AN XY: 26422

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

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.408

Alfa AF: 0.332 Hom.: 28848

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

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: rs12393998; hg19: chrX-119700082;