rs762094686

Variant names:

• chrX-120545526-GA-G
• rs762094686
• NM_001079872.2:c.847-10delT

Your query was ambiguous. Multiple possible variants found:

• chrX-120545526-GA-G
• chrX-120545526-GA-GAA
• chrX-120545526-GA-GAAA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001079872.2(CUL4B):​c.847-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,096,758 control chromosomes in the GnomAD database, including 6 homozygotes. There are 268 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (2 hom., 135 hem., cov: 22)
  • Exomes 𝑓: 0.00062 (4 hom. 133 hem.)
• Consequence: CUL4B NM_001079872.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.333
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant X-120545526-GA-G is Benign according to our data. Variant chrX-120545526-GA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 418559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00479 (520/108534) while in subpopulation AFR AF = 0.0163 (488/29872). AF 95% confidence interval is 0.0151. There are 2 homozygotes in GnomAd4. There are 135 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079872.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4B	NM_001079872.2	MANE Select	c.847-10delT		intron	N/A	NP_001073341.1
	CUL4B	NM_003588.4		c.901-10delT		intron	N/A	NP_003579.3
	CUL4B	NM_001330624.2		c.862-10delT		intron	N/A	NP_001317553.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4B	ENST00000371322.11	TSL:1 MANE Select	c.847-10delT		intron	N/A	ENSP00000360373.5
	CUL4B	ENST00000681206.1		c.961-10delT		intron	N/A	ENSP00000505480.1
	CUL4B	ENST00000680673.1		c.901-10delT		intron	N/A	ENSP00000505084.1

Frequencies

GnomAD3 genomes AF: 0.00476 AC: 516 AN: 108490 Hom.: 2 Cov.: 22

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00413

GnomAD2 exomes AF: 0.00146 AC: 165 AN: 112836 AF XY: 0.00109

Gnomad AFR exome AF: 0.0182

Gnomad AMR exome AF: 0.000718

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000325

Gnomad NFE exome AF: 0.000179

Gnomad OTH exome AF: 0.000989

GnomAD4 exome AF: 0.000622 AC: 615 AN: 988224 Hom.: 4 Cov.: 23 AF XY: 0.000463 AC XY: 133 AN XY: 286982

African (AFR) AF: 0.0175 AC: 419 AN: 24011

American (AMR) AF: 0.00119 AC: 34 AN: 28633

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17976

East Asian (EAS) AF: 0.0000355 AC: 1 AN: 28203

South Asian (SAS) AF: 0.0000626 AC: 3 AN: 47895

European-Finnish (FIN) AF: 0.0000796 AC: 3 AN: 37671

Middle Eastern (MID) AF: 0.00184 AC: 7 AN: 3795

European-Non Finnish (NFE) AF: 0.0000976 AC: 74 AN: 758012

Other (OTH) AF: 0.00176 AC: 74 AN: 42028

GnomAD4 genome AF: 0.00479 AC: 520 AN: 108534 Hom.: 2 Cov.: 22 AF XY: 0.00428 AC XY: 135 AN XY: 31566

African (AFR) AF: 0.0163 AC: 488 AN: 29872

American (AMR) AF: 0.00255 AC: 26 AN: 10184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2595

East Asian (EAS) AF: 0.00 AC: 0 AN: 3481

South Asian (SAS) AF: 0.00 AC: 0 AN: 2577

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52056

Other (OTH) AF: 0.00409 AC: 6 AN: 1468

Alfa AF: 0.00118 Hom.: 4

Bravo AF: 0.00546

Asia WGS AF: 0.00239 AC: 6 AN: 2518

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	X-linked intellectual disability Cabezas type (3)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs762094686; hg19: chrX-119679381;