X-120526946-C-T

Variant names:

• chrX-120526946-C-T
• rs5957406
• NM_001079872.2:c.2593-90G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079872.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4B	NM_001079872.2	MANE Select	c.2593-90G>A		intron	N/A	NP_001073341.1	Q13620-1
	CUL4B	NM_003588.4		c.2647-90G>A		intron	N/A	NP_003579.3
	CUL4B	NM_001330624.2		c.2608-90G>A		intron	N/A	NP_001317553.1	K4DI93

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4B	ENST00000371322.11	TSL:1 MANE Select	c.2593-90G>A		intron	N/A	ENSP00000360373.5	Q13620-1
	CUL4B	ENST00000681206.1		c.2707-90G>A		intron	N/A	ENSP00000505480.1	A0A7P0T954
	CUL4B	ENST00000680673.1		c.2647-90G>A		intron	N/A	ENSP00000505084.1	Q13620-2

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 6478 AN: 112091 Hom.: 488 Cov.: 23

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

African (AFR) AF: 0.210 AC: 2268 AN: 10790

American (AMR) AF: 0.0157 AC: 317 AN: 20165

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11030

East Asian (EAS) AF: 0.00 AC: 0 AN: 20825

South Asian (SAS) AF: 0.00143 AC: 42 AN: 29448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23685

Middle Eastern (MID) AF: 0.0127 AC: 29 AN: 2283

European-Non Finnish (NFE) AF: 0.000735 AC: 158 AN: 214821

Other (OTH) AF: 0.0194 AC: 367 AN: 18883

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

African (AFR) AF: 0.200 AC: 6152 AN: 30809

American (AMR) AF: 0.0214 AC: 227 AN: 10625

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3607

South Asian (SAS) AF: 0.00254 AC: 7 AN: 2759

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6053

Middle Eastern (MID) AF: 0.0372 AC: 8 AN: 215

European-Non Finnish (NFE) AF: 0.000846 AC: 45 AN: 53217

Other (OTH) AF: 0.0446 AC: 68 AN: 1523

Alfa AF: 0.0159 Hom.: 475

Bravo AF: 0.0674

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.63
DANN	Benign	0.65
PhyloP100		-0.37
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: rs5957406; hg19: chrX-119660801;