rs1556213268

Variant names:

• chrX-120544181-T-A
• NM_001079872.2:c.1106A>T

Your query was ambiguous. Multiple possible variants found:

• chrX-120544181-T-A
• chrX-120544181-T-C

Variant summary

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

The NM_001079872.2(CUL4B):​c.1106A>T​(p.Gln369Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000092 in 1,087,361 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: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: CUL4B NM_001079872.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.95

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]

LOC124905273 (HGNC:):

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.1106A>T	p.Gln369Leu	missense_variant	Exon 7 of 20	ENST00000371322.11	NP_001073341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL4B	ENST00000371322.11	c.1106A>T	p.Gln369Leu	missense_variant	Exon 7 of 20	1	NM_001079872.2	ENSP00000360373.5
CUL4B	ENST00000681206.1	c.1220A>T	p.Gln407Leu	missense_variant	Exon 10 of 23			ENSP00000505480.1
CUL4B	ENST00000680673.1	c.1160A>T	p.Gln387Leu	missense_variant	Exon 9 of 22			ENSP00000505084.1
CUL4B	ENST00000681253.1	c.1160A>T	p.Gln387Leu	missense_variant	Exon 10 of 23			ENSP00000506259.1
CUL4B	ENST00000681652.1	c.1160A>T	p.Gln387Leu	missense_variant	Exon 12 of 25			ENSP00000505176.1
CUL4B	ENST00000336592.11	c.1121A>T	p.Gln374Leu	missense_variant	Exon 8 of 21	5		ENSP00000338919.6
CUL4B	ENST00000674137.11	c.1106A>T	p.Gln369Leu	missense_variant	Exon 7 of 20			ENSP00000501019.6
CUL4B	ENST00000681090.1	c.1013A>T	p.Gln338Leu	missense_variant	Exon 7 of 20			ENSP00000506288.1
CUL4B	ENST00000404115.8	c.1106A>T	p.Gln369Leu	missense_variant	Exon 7 of 19	1		ENSP00000384109.4
CUL4B	ENST00000679927.1	c.761A>T	p.Gln254Leu	missense_variant	Exon 8 of 21			ENSP00000505603.1
CUL4B	ENST00000371323.3	c.572A>T	p.Gln191Leu	missense_variant	Exon 7 of 20	5		ENSP00000360374.3
CUL4B	ENST00000680474.1	c.548A>T	p.Gln183Leu	missense_variant	Exon 6 of 20			ENSP00000505562.1
CUL4B	ENST00000679844.1	c.548A>T	p.Gln183Leu	missense_variant	Exon 6 of 18			ENSP00000505239.1
CUL4B	ENST00000673919.1	n.*553A>T		non_coding_transcript_exon_variant	Exon 8 of 21			ENSP00000500994.1
CUL4B	ENST00000674073.2	n.548A>T		non_coding_transcript_exon_variant	Exon 6 of 18			ENSP00000501262.2
CUL4B	ENST00000679405.1	n.*315A>T		non_coding_transcript_exon_variant	Exon 9 of 22			ENSP00000504985.1
CUL4B	ENST00000679432.1	n.*315A>T		non_coding_transcript_exon_variant	Exon 9 of 22			ENSP00000505343.1
CUL4B	ENST00000680918.1	n.*22A>T		non_coding_transcript_exon_variant	Exon 5 of 18			ENSP00000505955.1
CUL4B	ENST00000681080.1	n.*315A>T		non_coding_transcript_exon_variant	Exon 7 of 20			ENSP00000505898.1
CUL4B	ENST00000681189.1	n.548A>T		non_coding_transcript_exon_variant	Exon 6 of 20			ENSP00000505973.1
CUL4B	ENST00000681333.1	n.1106A>T		non_coding_transcript_exon_variant	Exon 7 of 17			ENSP00000505739.1
CUL4B	ENST00000681869.1	n.548A>T		non_coding_transcript_exon_variant	Exon 6 of 17			ENSP00000505597.1
CUL4B	ENST00000681908.1	n.548A>T		non_coding_transcript_exon_variant	Exon 6 of 20			ENSP00000505777.1
CUL4B	ENST00000673919.1	n.*553A>T		3_prime_UTR_variant	Exon 8 of 21			ENSP00000500994.1
CUL4B	ENST00000679405.1	n.*315A>T		3_prime_UTR_variant	Exon 9 of 22			ENSP00000504985.1
CUL4B	ENST00000679432.1	n.*315A>T		3_prime_UTR_variant	Exon 9 of 22			ENSP00000505343.1
CUL4B	ENST00000680918.1	n.*22A>T		3_prime_UTR_variant	Exon 5 of 18			ENSP00000505955.1
CUL4B	ENST00000681080.1	n.*315A>T		3_prime_UTR_variant	Exon 7 of 20			ENSP00000505898.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.20e-7 AC: 1 AN: 1087361 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 353421

Gnomad4 AFR exome AF: 0.00

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: 0.00000120

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	0.00042	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.50	.;.;T;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Pathogenic	0.50	D
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.48	.;.;N;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.7	D;D;D;N
REVEL	Uncertain	0.33
Sift	Benign	0.24	T;T;T;T
Sift4G	Benign	0.26	T;T;T;.
Polyphen		0.0	B;.;B;.
Vest4		0.41
MutPred		0.40		.;.;Loss of disorder (P = 0.0377);.;
MVP		0.94
MPC		0.62
ClinPred		0.88	D
GERP RS		5.7
Varity_R		0.68
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-119678036;