ENST00000673919.1:n.*2687T>C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting

The ENST00000673919.1(CUL4B):n.*2687T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 111,820 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)

Consequence

CUL4B
ENST00000673919.1 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57

Publications

0 publications found

Variant links:

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]

CUL4B Gene-Disease associations (from GenCC):

X-linked intellectual disability, Cabezas type
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

CUL4B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000179 (2/111820) while in subpopulation EAS AF = 0.00056 (2/3570). AF 95% confidence interval is 0.0000986. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CUL4B	NM_001079872.2 link	c.*552T>C	3_prime_UTR_variant	Exon 20 of 20	ENST00000371322.11	NP_001073341.1	Q13620-1
CUL4B	NM_003588.4 link	c.*552T>C	3_prime_UTR_variant	Exon 22 of 22		NP_003579.3	Q13620-2
CUL4B	NM_001330624.2 link	c.*552T>C	3_prime_UTR_variant	Exon 21 of 21		NP_001317553.1	K4DI93
CUL4B	NM_001369145.1 link	c.*552T>C	3_prime_UTR_variant	Exon 20 of 20		NP_001356074.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CUL4B	ENST00000673919.1 link	n.*2687T>C	non_coding_transcript_exon_variant	Exon 21 of 21			ENSP00000500994.1	A0A669KAU9
CUL4B	ENST00000674073.2 link	n.*796T>C	non_coding_transcript_exon_variant	Exon 18 of 18			ENSP00000501262.2	A0A669KBG9
CUL4B	ENST00000679405.1 link	n.*2449T>C	non_coding_transcript_exon_variant	Exon 22 of 22			ENSP00000504985.1	A0A7P0Z439
CUL4B	ENST00000680918.1 link	n.*2156T>C	non_coding_transcript_exon_variant	Exon 18 of 18			ENSP00000505955.1	A0A7P0Z4G9
CUL4B	ENST00000681080.1 link	n.*2449T>C	non_coding_transcript_exon_variant	Exon 20 of 20			ENSP00000505898.1	A0A7P0Z4E4
CUL4B	ENST00000681189.1 link	n.*1406T>C	non_coding_transcript_exon_variant	Exon 20 of 20			ENSP00000505973.1	A0A7P0TAF9
CUL4B	ENST00000681333.1 link	n.*4133T>C	non_coding_transcript_exon_variant	Exon 17 of 17			ENSP00000505739.1	A0A7P0T9R8
CUL4B	ENST00000681908.1 link	n.*1412T>C	non_coding_transcript_exon_variant	Exon 20 of 20			ENSP00000505777.1	A0A7P0T9P5
CUL4B	ENST00000371322.11 link	c.*552T>C	3_prime_UTR_variant	Exon 20 of 20	1	NM_001079872.2	ENSP00000360373.5	Q13620-1
CUL4B	ENST00000681206.1 link	c.*552T>C	3_prime_UTR_variant	Exon 23 of 23			ENSP00000505480.1	A0A7P0T954
CUL4B	ENST00000680673.1 link	c.*552T>C	3_prime_UTR_variant	Exon 22 of 22			ENSP00000505084.1	Q13620-2
CUL4B	ENST00000681253.1 link	c.*552T>C	3_prime_UTR_variant	Exon 23 of 23			ENSP00000506259.1	Q13620-2
CUL4B	ENST00000681652.1 link	c.*552T>C	3_prime_UTR_variant	Exon 25 of 25			ENSP00000505176.1	Q13620-2
CUL4B	ENST00000336592.11 link	c.*552T>C	3_prime_UTR_variant	Exon 21 of 21	5		ENSP00000338919.6	K4DI93
CUL4B	ENST00000674137.11 link	c.*552T>C	3_prime_UTR_variant	Exon 20 of 20			ENSP00000501019.6	A0A669KAX4
CUL4B	ENST00000681090.1 link	c.*552T>C	3_prime_UTR_variant	Exon 20 of 20			ENSP00000506288.1	A0A7P0TAQ3
CUL4B	ENST00000679927.1 link	c.*552T>C	3_prime_UTR_variant	Exon 21 of 21			ENSP00000505603.1	A0A7P0T9L3
CUL4B	ENST00000371323.3 link	c.*552T>C	3_prime_UTR_variant	Exon 20 of 20	5		ENSP00000360374.3	Q13620-3
CUL4B	ENST00000679844.1 link	c.*552T>C	3_prime_UTR_variant	Exon 18 of 18			ENSP00000505239.1	A0A7P0T8P8
CUL4B	ENST00000673919.1 link	n.*2687T>C	3_prime_UTR_variant	Exon 21 of 21			ENSP00000500994.1	A0A669KAU9
CUL4B	ENST00000674073.2 link	n.*796T>C	3_prime_UTR_variant	Exon 18 of 18			ENSP00000501262.2	A0A669KBG9
CUL4B	ENST00000679405.1 link	n.*2449T>C	3_prime_UTR_variant	Exon 22 of 22			ENSP00000504985.1	A0A7P0Z439
CUL4B	ENST00000680918.1 link	n.*2156T>C	3_prime_UTR_variant	Exon 18 of 18			ENSP00000505955.1	A0A7P0Z4G9
CUL4B	ENST00000681080.1 link	n.*2449T>C	3_prime_UTR_variant	Exon 20 of 20			ENSP00000505898.1	A0A7P0Z4E4
CUL4B	ENST00000681189.1 link	n.*1406T>C	3_prime_UTR_variant	Exon 20 of 20			ENSP00000505973.1	A0A7P0TAF9
CUL4B	ENST00000681333.1 link	n.*4133T>C	3_prime_UTR_variant	Exon 17 of 17			ENSP00000505739.1	A0A7P0T9R8
CUL4B	ENST00000681908.1 link	n.*1412T>C	3_prime_UTR_variant	Exon 20 of 20			ENSP00000505777.1	A0A7P0T9P5
CUL4B	ENST00000680474.1 link	c.*686T>C	downstream_gene_variant				ENSP00000505562.1	A0A7P0T9C8
CUL4B	ENST00000679432.1 link	n.*2449T>C	downstream_gene_variant				ENSP00000505343.1	A0A7P0T8W4

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111769

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000279

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111820

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

33992

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30848

American (AMR)

AF:

0.00

AC:

AN:

10496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.000560

AC:

AN:

3570

South Asian (SAS)

AF:

0.00

AC:

AN:

2695

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6015

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53139

Other (OTH)

AF:

0.00

AC:

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Feb 17, 2022

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

1.6

Splicing

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

Publications

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ENST00000673919.1:n.*2687T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over