X-120545526-GA-GAA

Position:

• chrX-120545526-GA-GAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001079872.2(CUL4B):​c.847-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000402 in 983,910 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.00040 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: CUL4B NM_001079872.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000402 (396/983910) while in subpopulation MID AF= 0.000528 (2/3785). AF 95% confidence interval is 0.000416. There are 0 homozygotes in gnomad4_exome. There are 2 alleles in male gnomad4_exome subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUL4B	NM_001079872.2	c.847-10dupT		intron_variant		ENST00000371322.11	NP_001073341.1
CUL4B	NM_003588.4	c.901-10dupT		intron_variant			NP_003579.3
CUL4B	NM_001330624.2	c.862-10dupT		intron_variant			NP_001317553.1
CUL4B	NM_001369145.1	c.313-10dupT		intron_variant			NP_001356074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL4B	ENST00000371322.11	c.847-10dupT		intron_variant		1	NM_001079872.2	ENSP00000360373.5
CUL4B	ENST00000681206.1	c.961-10dupT		intron_variant				ENSP00000505480.1
CUL4B	ENST00000680673.1	c.901-10dupT		intron_variant				ENSP00000505084.1
CUL4B	ENST00000681253.1	c.901-10dupT		intron_variant				ENSP00000506259.1
CUL4B	ENST00000681652.1	c.901-10dupT		intron_variant				ENSP00000505176.1
CUL4B	ENST00000336592.11	c.862-10dupT		intron_variant		5		ENSP00000338919.6
CUL4B	ENST00000674137.11	c.847-10dupT		intron_variant				ENSP00000501019.6
CUL4B	ENST00000681090.1	c.847-10dupT		intron_variant				ENSP00000506288.1
CUL4B	ENST00000404115.8	c.847-10dupT		intron_variant		1		ENSP00000384109.4
CUL4B	ENST00000679927.1	c.502-10dupT		intron_variant				ENSP00000505603.1
CUL4B	ENST00000371323.3	c.313-10dupT		intron_variant		5		ENSP00000360374.3
CUL4B	ENST00000680474.1	c.289-10dupT		intron_variant				ENSP00000505562.1
CUL4B	ENST00000679844.1	c.289-10dupT		intron_variant				ENSP00000505239.1
CUL4B	ENST00000673919.1	n.*294-10dupT		intron_variant				ENSP00000500994.1
CUL4B	ENST00000674073.2	n.289-10dupT		intron_variant				ENSP00000501262.2
CUL4B	ENST00000679405.1	n.*56-10dupT		intron_variant				ENSP00000504985.1
CUL4B	ENST00000679432.1	n.*56-10dupT		intron_variant				ENSP00000505343.1
CUL4B	ENST00000680918.1	n.289-10dupT		intron_variant				ENSP00000505955.1
CUL4B	ENST00000681080.1	n.*56-10dupT		intron_variant				ENSP00000505898.1
CUL4B	ENST00000681189.1	n.289-10dupT		intron_variant				ENSP00000505973.1
CUL4B	ENST00000681333.1	n.847-10dupT		intron_variant				ENSP00000505739.1
CUL4B	ENST00000681869.1	n.289-10dupT		intron_variant				ENSP00000505597.1
CUL4B	ENST00000681908.1	n.289-10dupT		intron_variant				ENSP00000505777.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 108474 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 31496 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000402 AC: 396 AN: 983910 Hom.: 0 Cov.: 23 AF XY: 0.00000703 AC XY: 2 AN XY: 284644

Gnomad4 AFR exome AF: 0.000293

Gnomad4 AMR exome AF: 0.0000350

Gnomad4 ASJ exome AF: 0.000391

Gnomad4 EAS exome AF: 0.000213

Gnomad4 SAS exome AF: 0.000230

Gnomad4 FIN exome AF: 0.0000797

Gnomad4 NFE exome AF: 0.000456

Gnomad4 OTH exome AF: 0.000358

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 108474 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 31496

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs762094686; hg19: chrX-119679381;