chrX-120538193-G-A

Variant names:

• chrX-120538193-G-A
• rs1556199319
• NM_001079872.2:c.1869C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001079872.2(CUL4B):​c.1869C>T​(p.Phe623Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000937 in 1,067,518 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: CUL4B NM_001079872.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.64
• 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

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=-0.45).
• BP6: Variant X-120538193-G-A is Benign according to our data. Variant chrX-120538193-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 434870.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4B	NM_001079872.2	MANE Select	c.1869C>T	p.Phe623Phe	synonymous	Exon 14 of 20	NP_001073341.1
	CUL4B	NM_003588.4		c.1923C>T	p.Phe641Phe	synonymous	Exon 16 of 22	NP_003579.3
	CUL4B	NM_001330624.2		c.1884C>T	p.Phe628Phe	synonymous	Exon 15 of 21	NP_001317553.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4B	ENST00000371322.11	TSL:1 MANE Select	c.1869C>T	p.Phe623Phe	synonymous	Exon 14 of 20	ENSP00000360373.5
	CUL4B	ENST00000681206.1		c.1983C>T	p.Phe661Phe	synonymous	Exon 17 of 23	ENSP00000505480.1
	CUL4B	ENST00000680673.1		c.1923C>T	p.Phe641Phe	synonymous	Exon 16 of 22	ENSP00000505084.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.37e-7 AC: 1 AN: 1067518 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 336330

African (AFR) AF: 0.00 AC: 0 AN: 25821

American (AMR) AF: 0.00 AC: 0 AN: 34997

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19147

East Asian (EAS) AF: 0.00 AC: 0 AN: 29961

South Asian (SAS) AF: 0.0000188 AC: 1 AN: 53134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 815334

Other (OTH) AF: 0.00 AC: 0 AN: 45018

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 11, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.2
DANN	Benign	0.63
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism

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: rs1556199319; hg19: chrX-119672048;