rs5957406

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-120526946-C-A
• chrX-120526946-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001079872.2(CUL4B):​c.2593-90G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: CUL4B NM_001079872.2 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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>T		intron	N/A	NP_001073341.1	Q13620-1
	CUL4B	NM_003588.4		c.2647-90G>T		intron	N/A	NP_003579.3
	CUL4B	NM_001330624.2		c.2608-90G>T		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>T		intron	N/A	ENSP00000360373.5	Q13620-1
	CUL4B	ENST00000681206.1		c.2707-90G>T		intron	N/A	ENSP00000505480.1	A0A7P0T954
	CUL4B	ENST00000680673.1		c.2647-90G>T		intron	N/A	ENSP00000505084.1	Q13620-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 351944 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 91248

African (AFR) AF: 0.00 AC: 0 AN: 10802

American (AMR) AF: 0.00 AC: 0 AN: 20163

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 29448

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2283

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 214825

Other (OTH) AF: 0.00 AC: 0 AN: 18883

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.51
DANN	Benign	0.58
PhyloP100		-0.37

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;