X-120526946-C-T

Position:

• chrX-120526946-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• 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 -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
CUL4B	NM_001079872.2	c.2593-90G>A		intron_variant		ENST00000371322.11	NP_001073341.1
CUL4B	NM_003588.4	c.2647-90G>A		intron_variant			NP_003579.3
CUL4B	NM_001330624.2	c.2608-90G>A		intron_variant			NP_001317553.1
CUL4B	NM_001369145.1	c.2059-90G>A		intron_variant			NP_001356074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL4B	ENST00000371322.11	c.2593-90G>A		intron_variant		1	NM_001079872.2	ENSP00000360373.5
CUL4B	ENST00000681206.1	c.2707-90G>A		intron_variant				ENSP00000505480.1
CUL4B	ENST00000680673.1	c.2647-90G>A		intron_variant				ENSP00000505084.1
CUL4B	ENST00000681253.1	c.2647-90G>A		intron_variant				ENSP00000506259.1
CUL4B	ENST00000681652.1	c.2647-90G>A		intron_variant				ENSP00000505176.1
CUL4B	ENST00000336592.11	c.2608-90G>A		intron_variant		5		ENSP00000338919.6
CUL4B	ENST00000674137.11	c.2599-90G>A		intron_variant				ENSP00000501019.6
CUL4B	ENST00000681090.1	c.2500-90G>A		intron_variant				ENSP00000506288.1
CUL4B	ENST00000404115.8	c.2440-90G>A		intron_variant		1		ENSP00000384109.4
CUL4B	ENST00000679927.1	c.2248-90G>A		intron_variant				ENSP00000505603.1
CUL4B	ENST00000371323.3	c.2059-90G>A		intron_variant		5		ENSP00000360374.3
CUL4B	ENST00000680474.1	c.*39-90G>A		intron_variant				ENSP00000505562.1
CUL4B	ENST00000679844.1	c.1930-90G>A		intron_variant				ENSP00000505239.1
CUL4B	ENST00000673919.1	n.*2040-90G>A		intron_variant				ENSP00000500994.1
CUL4B	ENST00000674073.2	n.*149-90G>A		intron_variant				ENSP00000501262.2
CUL4B	ENST00000679405.1	n.*1802-90G>A		intron_variant				ENSP00000504985.1
CUL4B	ENST00000679432.1	n.*1802-90G>A		intron_variant				ENSP00000505343.1
CUL4B	ENST00000680918.1	n.*1509-90G>A		intron_variant				ENSP00000505955.1
CUL4B	ENST00000681080.1	n.*1802-90G>A		intron_variant				ENSP00000505898.1
CUL4B	ENST00000681189.1	n.*759-90G>A		intron_variant				ENSP00000505973.1
CUL4B	ENST00000681333.1	n.*3486-90G>A		intron_variant				ENSP00000505739.1
CUL4B	ENST00000681908.1	n.*765-90G>A		intron_variant				ENSP00000505777.1

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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;