X-120545526-GA-GAAA

Variant names:

• chrX-120545526-G-GAA
• NM_001079872.2:c.847-11_847-10dupTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001079872.2(CUL4B):​c.847-11_847-10dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 989,825 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000010 (0 hom. 0 hem.)
• 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL4B	NM_001079872.2	c.847-11_847-10dupTT		intron_variant	Intron 4 of 19	ENST00000371322.11	NP_001073341.1
CUL4B	NM_003588.4	c.901-11_901-10dupTT		intron_variant	Intron 6 of 21		NP_003579.3
CUL4B	NM_001330624.2	c.862-11_862-10dupTT		intron_variant	Intron 5 of 20		NP_001317553.1
CUL4B	NM_001369145.1	c.313-11_313-10dupTT		intron_variant	Intron 4 of 19		NP_001356074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL4B	ENST00000371322.11	c.847-10_847-9insTT		intron_variant	Intron 4 of 19	1	NM_001079872.2	ENSP00000360373.5
CUL4B	ENST00000681206.1	c.961-10_961-9insTT		intron_variant	Intron 7 of 22			ENSP00000505480.1
CUL4B	ENST00000680673.1	c.901-10_901-9insTT		intron_variant	Intron 6 of 21			ENSP00000505084.1
CUL4B	ENST00000681253.1	c.901-10_901-9insTT		intron_variant	Intron 7 of 22			ENSP00000506259.1
CUL4B	ENST00000681652.1	c.901-10_901-9insTT		intron_variant	Intron 9 of 24			ENSP00000505176.1
CUL4B	ENST00000336592.11	c.862-10_862-9insTT		intron_variant	Intron 5 of 20	5		ENSP00000338919.6
CUL4B	ENST00000674137.11	c.847-10_847-9insTT		intron_variant	Intron 4 of 19			ENSP00000501019.6
CUL4B	ENST00000681090.1	c.847-10_847-9insTT		intron_variant	Intron 4 of 19			ENSP00000506288.1
CUL4B	ENST00000404115.8	c.847-10_847-9insTT		intron_variant	Intron 4 of 18	1		ENSP00000384109.4
CUL4B	ENST00000679927.1	c.502-10_502-9insTT		intron_variant	Intron 5 of 20			ENSP00000505603.1
CUL4B	ENST00000371323.3	c.313-10_313-9insTT		intron_variant	Intron 4 of 19	5		ENSP00000360374.3
CUL4B	ENST00000680474.1	c.289-10_289-9insTT		intron_variant	Intron 3 of 19			ENSP00000505562.1
CUL4B	ENST00000679844.1	c.289-10_289-9insTT		intron_variant	Intron 3 of 17			ENSP00000505239.1
CUL4B	ENST00000673919.1	n.*294-10_*294-9insTT		intron_variant	Intron 5 of 20			ENSP00000500994.1
CUL4B	ENST00000674073.2	n.289-10_289-9insTT		intron_variant	Intron 3 of 17			ENSP00000501262.2
CUL4B	ENST00000679405.1	n.*56-10_*56-9insTT		intron_variant	Intron 6 of 21			ENSP00000504985.1
CUL4B	ENST00000679432.1	n.*56-10_*56-9insTT		intron_variant	Intron 6 of 21			ENSP00000505343.1
CUL4B	ENST00000680918.1	n.289-10_289-9insTT		intron_variant	Intron 3 of 17			ENSP00000505955.1
CUL4B	ENST00000681080.1	n.*56-10_*56-9insTT		intron_variant	Intron 4 of 19			ENSP00000505898.1
CUL4B	ENST00000681189.1	n.289-10_289-9insTT		intron_variant	Intron 3 of 19			ENSP00000505973.1
CUL4B	ENST00000681333.1	n.847-10_847-9insTT		intron_variant	Intron 4 of 16			ENSP00000505739.1
CUL4B	ENST00000681869.1	n.289-10_289-9insTT		intron_variant	Intron 3 of 16			ENSP00000505597.1
CUL4B	ENST00000681908.1	n.289-10_289-9insTT		intron_variant	Intron 3 of 19			ENSP00000505777.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000101 AC: 1 AN: 989825 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 288071

Gnomad4 AFR exome AF: 0.0000416

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-119679381;