NM_001079872.2:c.372_377dupCTCCTC

Variant names:

• chrX-120560261-T-TGAGGAG
• rs754330779
• NM_001079872.2:c.372_377dupCTCCTC

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

The NM_001079872.2(CUL4B):​c.372_377dupCTCCTC​(p.Ser125_Ser126dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00000901 in 111,015 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: 𝑓 0.0000090 (0 hom., 0 hem., cov: 22)
• Consequence: CUL4B NM_001079872.2 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.84

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_001079872.2

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL4B	NM_001079872.2	c.372_377dupCTCCTC	p.Ser125_Ser126dup	disruptive_inframe_insertion	Exon 1 of 20	ENST00000371322.11	NP_001073341.1
CUL4B	NM_003588.4	c.426_431dupCTCCTC	p.Ser143_Ser144dup	disruptive_inframe_insertion	Exon 3 of 22		NP_003579.3
CUL4B	NM_001330624.2	c.387_392dupCTCCTC	p.Ser130_Ser131dup	disruptive_inframe_insertion	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_377dupCTCCTC	p.Ser125_Ser126dup	disruptive_inframe_insertion	Exon 1 of 20	1	NM_001079872.2	ENSP00000360373.5
CUL4B	ENST00000681206.1	c.387_392dupCTCCTC	p.Ser130_Ser131dup	disruptive_inframe_insertion	Exon 2 of 23			ENSP00000505480.1
CUL4B	ENST00000680673.1	c.426_431dupCTCCTC	p.Ser143_Ser144dup	disruptive_inframe_insertion	Exon 3 of 22			ENSP00000505084.1
CUL4B	ENST00000681253.1	c.426_431dupCTCCTC	p.Ser143_Ser144dup	disruptive_inframe_insertion	Exon 4 of 23			ENSP00000506259.1
CUL4B	ENST00000681652.1	c.426_431dupCTCCTC	p.Ser143_Ser144dup	disruptive_inframe_insertion	Exon 6 of 25			ENSP00000505176.1
CUL4B	ENST00000336592.11	c.387_392dupCTCCTC	p.Ser130_Ser131dup	disruptive_inframe_insertion	Exon 2 of 21	5		ENSP00000338919.6
CUL4B	ENST00000674137.11	c.372_377dupCTCCTC	p.Ser125_Ser126dup	disruptive_inframe_insertion	Exon 1 of 20			ENSP00000501019.6
CUL4B	ENST00000681090.1	c.372_377dupCTCCTC	p.Ser125_Ser126dup	disruptive_inframe_insertion	Exon 1 of 20			ENSP00000506288.1
CUL4B	ENST00000404115.8	c.372_377dupCTCCTC	p.Ser125_Ser126dup	disruptive_inframe_insertion	Exon 1 of 19	1		ENSP00000384109.4
CUL4B	ENST00000679927.1	c.27_32dupCTCCTC	p.Ser10_Ser11dup	disruptive_inframe_insertion	Exon 2 of 21			ENSP00000505603.1
CUL4B	ENST00000673919.1	n.372_377dupCTCCTC		non_coding_transcript_exon_variant	Exon 1 of 21			ENSP00000500994.1
CUL4B	ENST00000679432.1	n.357_362dupCTCCTC		non_coding_transcript_exon_variant	Exon 1 of 22			ENSP00000505343.1
CUL4B	ENST00000681333.1	n.372_377dupCTCCTC		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000505739.1

Frequencies

GnomAD3 genomes AF: 0.00000901 AC: 1 AN: 111015 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33341

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: 0.000170

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000901 AC: 1 AN: 111015 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33341

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: 0.000170

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;