X-120526946-C-T

Position:

• chrX-120526946-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001079872.2(CUL4B):​c.2593-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 464,073 control chromosomes in the GnomAD database, including 690 homozygotes. There are 2,489 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.058 (491 hom., 1796 hem., cov: 23)
  • Exomes 𝑓: 0.0090 (199 hom. 693 hem.)
• Consequence: CUL4B NM_001079872.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.372

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant X-120526946-C-T is Benign according to our data. Variant chrX-120526946-C-T is described in ClinVar as [Benign]. Clinvar id is 1222218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUL4B	NM_001079872.2	c.2593-90G>A		intron_variant		ENST00000371322.11
CUL4B	NM_001330624.2	c.2608-90G>A		intron_variant
CUL4B	NM_001369145.1	c.2059-90G>A		intron_variant
CUL4B	NM_003588.4	c.2647-90G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUL4B	ENST00000371322.11	c.2593-90G>A		intron_variant		1	NM_001079872.2

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 6478 AN: 112091 Hom.: 488 Cov.: 23 AF XY: 0.0517 AC XY: 1775 AN XY: 34347

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00253

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.000845

Gnomad OTH AF: 0.0445

GnomAD4 exome AF: 0.00904 AC: 3181 AN: 351930 Hom.: 199 AF XY: 0.00759 AC XY: 693 AN XY: 91246

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.0157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00143

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000735

Gnomad4 OTH exome AF: 0.0194

GnomAD4 genome AF: 0.0580 AC: 6507 AN: 112143 Hom.: 491 Cov.: 23 AF XY: 0.0522 AC XY: 1796 AN XY: 34409

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.0214

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00254

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000846

Gnomad4 OTH AF: 0.0446

Alfa AF: 0.0132 Hom.: 346

Bravo AF: 0.0674

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.63
DANN	Benign	0.65

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: rs5957406; hg19: chrX-119660801;