chrX-120560261-TGAGGAG-T

Variant names:

• chrX-120560261-TGAGGAG-T
• rs754330779
• NM_001079872.2:c.372_377delCTCCTC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3 BS2

The NM_001079872.2(CUL4B):​c.372_377delCTCCTC​(p.Ser125_Ser126del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000456 in 1,097,166 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: not found (cov: 22)
  • Exomes 𝑓: 0.0000046 (0 hom. 2 hem.)
• Consequence: CUL4B NM_001079872.2 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.04

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 Likely_benign. Variant got -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001079872.2
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL4B	NM_001079872.2	c.372_377delCTCCTC	p.Ser125_Ser126del	disruptive_inframe_deletion	Exon 1 of 20	ENST00000371322.11	NP_001073341.1
CUL4B	NM_003588.4	c.426_431delCTCCTC	p.Ser143_Ser144del	disruptive_inframe_deletion	Exon 3 of 22		NP_003579.3
CUL4B	NM_001330624.2	c.387_392delCTCCTC	p.Ser130_Ser131del	disruptive_inframe_deletion	Exon 2 of 21		NP_001317553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL4B	ENST00000371322.11	c.372_377delCTCCTC	p.Ser125_Ser126del	disruptive_inframe_deletion	Exon 1 of 20	1	NM_001079872.2	ENSP00000360373.5
CUL4B	ENST00000681206.1	c.387_392delCTCCTC	p.Ser130_Ser131del	disruptive_inframe_deletion	Exon 2 of 23			ENSP00000505480.1
CUL4B	ENST00000680673.1	c.426_431delCTCCTC	p.Ser143_Ser144del	disruptive_inframe_deletion	Exon 3 of 22			ENSP00000505084.1
CUL4B	ENST00000681253.1	c.426_431delCTCCTC	p.Ser143_Ser144del	disruptive_inframe_deletion	Exon 4 of 23			ENSP00000506259.1
CUL4B	ENST00000681652.1	c.426_431delCTCCTC	p.Ser143_Ser144del	disruptive_inframe_deletion	Exon 6 of 25			ENSP00000505176.1
CUL4B	ENST00000336592.11	c.387_392delCTCCTC	p.Ser130_Ser131del	disruptive_inframe_deletion	Exon 2 of 21	5		ENSP00000338919.6
CUL4B	ENST00000674137.11	c.372_377delCTCCTC	p.Ser125_Ser126del	disruptive_inframe_deletion	Exon 1 of 20			ENSP00000501019.6
CUL4B	ENST00000681090.1	c.372_377delCTCCTC	p.Ser125_Ser126del	disruptive_inframe_deletion	Exon 1 of 20			ENSP00000506288.1
CUL4B	ENST00000404115.8	c.372_377delCTCCTC	p.Ser125_Ser126del	disruptive_inframe_deletion	Exon 1 of 19	1		ENSP00000384109.4
CUL4B	ENST00000679927.1	c.27_32delCTCCTC	p.Ser10_Ser11del	disruptive_inframe_deletion	Exon 2 of 21			ENSP00000505603.1
CUL4B	ENST00000673919.1	n.372_377delCTCCTC		non_coding_transcript_exon_variant	Exon 1 of 21			ENSP00000500994.1
CUL4B	ENST00000679432.1	n.357_362delCTCCTC		non_coding_transcript_exon_variant	Exon 1 of 22			ENSP00000505343.1
CUL4B	ENST00000681333.1	n.372_377delCTCCTC		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000505739.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.0000116 AC: 2 AN: 173145 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 61627

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000775

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000456 AC: 5 AN: 1097166 Hom.: 0 AF XY: 0.00000551 AC XY: 2 AN XY: 362892

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000568

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000370

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

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

LitVar

Other links and lift over

dbSNP: rs754330779; hg19: chrX-119694116;