rs1556199319

Variant names:

• chrX-120538193-G-A
• rs1556199319
• NM_001079872.2:c.1869C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001079872.2(CUL4B):​c.1869C>T​(p.Phe623Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000937 in 1,067,518 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: CUL4B NM_001079872.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.64

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant X-120538193-G-A is Benign according to our data. Variant chrX-120538193-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 434870.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL4B	NM_001079872.2	c.1869C>T	p.Phe623Phe	synonymous_variant	Exon 14 of 20	ENST00000371322.11	NP_001073341.1
CUL4B	NM_003588.4	c.1923C>T	p.Phe641Phe	synonymous_variant	Exon 16 of 22		NP_003579.3
CUL4B	NM_001330624.2	c.1884C>T	p.Phe628Phe	synonymous_variant	Exon 15 of 21		NP_001317553.1
CUL4B	NM_001369145.1	c.1335C>T	p.Phe445Phe	synonymous_variant	Exon 14 of 20		NP_001356074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL4B	ENST00000371322.11	c.1869C>T	p.Phe623Phe	synonymous_variant	Exon 14 of 20	1	NM_001079872.2	ENSP00000360373.5
CUL4B	ENST00000681206.1	c.1983C>T	p.Phe661Phe	synonymous_variant	Exon 17 of 23			ENSP00000505480.1
CUL4B	ENST00000680673.1	c.1923C>T	p.Phe641Phe	synonymous_variant	Exon 16 of 22			ENSP00000505084.1
CUL4B	ENST00000681253.1	c.1923C>T	p.Phe641Phe	synonymous_variant	Exon 17 of 23			ENSP00000506259.1
CUL4B	ENST00000681652.1	c.1923C>T	p.Phe641Phe	synonymous_variant	Exon 19 of 25			ENSP00000505176.1
CUL4B	ENST00000336592.11	c.1884C>T	p.Phe628Phe	synonymous_variant	Exon 15 of 21	5		ENSP00000338919.6
CUL4B	ENST00000674137.11	c.1869C>T	p.Phe623Phe	synonymous_variant	Exon 14 of 20			ENSP00000501019.6
CUL4B	ENST00000681090.1	c.1776C>T	p.Phe592Phe	synonymous_variant	Exon 14 of 20			ENSP00000506288.1
CUL4B	ENST00000404115.8	c.1869C>T	p.Phe623Phe	synonymous_variant	Exon 14 of 19	1		ENSP00000384109.4
CUL4B	ENST00000679927.1	c.1524C>T	p.Phe508Phe	synonymous_variant	Exon 15 of 21			ENSP00000505603.1
CUL4B	ENST00000371323.3	c.1335C>T	p.Phe445Phe	synonymous_variant	Exon 14 of 20	5		ENSP00000360374.3
CUL4B	ENST00000680474.1	c.1311C>T	p.Phe437Phe	synonymous_variant	Exon 13 of 20			ENSP00000505562.1
CUL4B	ENST00000679844.1	c.1206C>T	p.Phe402Phe	synonymous_variant	Exon 12 of 18			ENSP00000505239.1
CUL4B	ENST00000673919.1	n.*1316C>T		non_coding_transcript_exon_variant	Exon 15 of 21			ENSP00000500994.1
CUL4B	ENST00000674073.2	n.1311C>T		non_coding_transcript_exon_variant	Exon 13 of 18			ENSP00000501262.2
CUL4B	ENST00000679405.1	n.*1078C>T		non_coding_transcript_exon_variant	Exon 16 of 22			ENSP00000504985.1
CUL4B	ENST00000679432.1	n.*1078C>T		non_coding_transcript_exon_variant	Exon 16 of 22			ENSP00000505343.1
CUL4B	ENST00000680918.1	n.*785C>T		non_coding_transcript_exon_variant	Exon 12 of 18			ENSP00000505955.1
CUL4B	ENST00000681080.1	n.*1078C>T		non_coding_transcript_exon_variant	Exon 14 of 20			ENSP00000505898.1
CUL4B	ENST00000681189.1	n.*35C>T		non_coding_transcript_exon_variant	Exon 14 of 20			ENSP00000505973.1
CUL4B	ENST00000681333.1	n.*2762C>T		non_coding_transcript_exon_variant	Exon 11 of 17			ENSP00000505739.1
CUL4B	ENST00000681869.1	n.1311C>T		non_coding_transcript_exon_variant	Exon 13 of 17			ENSP00000505597.1
CUL4B	ENST00000681908.1	n.1311C>T		non_coding_transcript_exon_variant	Exon 13 of 20			ENSP00000505777.1
CUL4B	ENST00000673919.1	n.*1316C>T		3_prime_UTR_variant	Exon 15 of 21			ENSP00000500994.1
CUL4B	ENST00000679405.1	n.*1078C>T		3_prime_UTR_variant	Exon 16 of 22			ENSP00000504985.1
CUL4B	ENST00000679432.1	n.*1078C>T		3_prime_UTR_variant	Exon 16 of 22			ENSP00000505343.1
CUL4B	ENST00000680918.1	n.*785C>T		3_prime_UTR_variant	Exon 12 of 18			ENSP00000505955.1
CUL4B	ENST00000681080.1	n.*1078C>T		3_prime_UTR_variant	Exon 14 of 20			ENSP00000505898.1
CUL4B	ENST00000681189.1	n.*35C>T		3_prime_UTR_variant	Exon 14 of 20			ENSP00000505973.1
CUL4B	ENST00000681333.1	n.*2762C>T		3_prime_UTR_variant	Exon 11 of 17			ENSP00000505739.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.37e-7 AC: 1 AN: 1067518 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 336330

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: 0.0000188

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 11, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.2
DANN	Benign	0.63

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: rs1556199319; hg19: chrX-119672048;