CRYBB3

crystallin beta B3, the group of Beta-gamma crystallins

Basic information

Region (hg38): 22:25199857-25207359

Previous symbols: [ "CRYB3" ]

Links

ENSG00000100053 ∙ NCBI:1417 ∙ OMIM:123630 ∙ HGNC:2400 ∙ Uniprot:P26998 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cataract 22 multiple types (Definitive), mode of inheritance: AR
• cataract 22 multiple types (Moderate), mode of inheritance: Semidominant
• early-onset anterior polar cataract (Supportive), mode of inheritance: AD
• early-onset nuclear cataract (Supportive), mode of inheritance: AD
• cataract 22 multiple types (Strong), mode of inheritance: AR
• cataract 22 multiple types (Strong), mode of inheritance: AD
• cataract 22 multiple types (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 22, multiple types	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	15914629; 27326458; 28418495; 23508780

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CRYBB3 gene.

• Cataract 22 multiple types (53 variants)
• not provided (28 variants)
• Inborn genetic diseases (20 variants)
• Congenital nuclear cataract (7 variants)
• not specified (3 variants)
• CRYBB3-related condition (1 variants)
• Cataract;Microphthalmia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRYBB3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	4		8
missense	1	1	34	2	1	39
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			3	1		4
non coding			5	7	11	23
Total	1	1	44	13	12

Variants in CRYBB3

This is a list of pathogenic ClinVar variants found in the CRYBB3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-25199869-C-T		Cataract 22 multiple types	Uncertain significance (Jan 13, 2018)
22-25199873-C-G		Cataract 22 multiple types	Uncertain significance (Jan 13, 2018)
22-25201364-T-C		Congenital nuclear cataract • Cataract 22 multiple types	Benign (Jul 30, 2021)
22-25201401-C-T		Inborn genetic diseases	Uncertain significance (Dec 06, 2021)
22-25201402-G-A		Cataract 22 multiple types	Benign/Likely benign (Dec 22, 2022)
22-25201404-A-G		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
22-25201421-G-A		Cataract 22 multiple types	Uncertain significance (Jan 13, 2018)
22-25201434-C-G		Congenital nuclear cataract • Cataract 22 multiple types • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 01, 2022)
22-25201447-T-C		Cataract 22 multiple types	Likely benign (Sep 23, 2021)
22-25201478-G-C		Cataract 22 multiple types	Likely benign (Oct 31, 2022)
22-25201489-G-A		Cataract 22 multiple types	Likely benign (May 25, 2023)
22-25201659-C-T			Benign (May 15, 2019)
22-25201744-C-CAT			Benign (Jul 27, 2018)
22-25202375-C-T			Likely benign (May 28, 2019)
22-25202694-G-T		Cataract 22 multiple types • Inborn genetic diseases	Conflicting classifications of pathogenicity (Apr 29, 2023)
22-25202697-C-T		Cataract 22 multiple types	Benign (Apr 29, 2023)
22-25202710-C-T		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
22-25202714-G-T		Cataract 22 multiple types	Uncertain significance (Jan 27, 2022)
22-25202723-C-T		Cataract 22 multiple types • Inborn genetic diseases	Conflicting classifications of pathogenicity (Oct 31, 2022)
22-25202734-C-T		Cataract 22 multiple types	Uncertain significance (Jan 12, 2018)
22-25202742-G-A		Cataract 22 multiple types	Uncertain significance (Jan 12, 2018)
22-25202746-G-T		Inborn genetic diseases	Uncertain significance (Jun 26, 2023)
22-25202755-C-A		Cataract 22 multiple types	Uncertain significance (Mar 09, 2022)
22-25202756-T-TGTC		Cataract 22 multiple types	Uncertain significance (Jan 04, 2024)
22-25202772-C-T		Cataract 22 multiple types	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRYBB3	protein_coding	protein_coding	ENST00000215855	5	7514

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.58e-11	0.0255	125354	2	392	125748	0.00157

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.126	151	147	1.03	0.0000111	1392
Missense in Polyphen		46	52.782	0.87151		521
Synonymous	-0.461	58	53.7	1.08	0.00000386	392
Loss of Function	-0.462	15	13.2	1.14	7.74e-7	115

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00590	0.00580
Ashkenazi Jewish	0.0190	0.0190
East Asian	0.00169	0.00169
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000434	0.000431
Middle Eastern	0.00169	0.00169
South Asian	0.000294	0.000294
Other	0.00213	0.00212

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Crystallins are the dominant structural components of the vertebrate eye lens.
• Disease: DISEASE: Cataract 22, multiple types (CTRCT22) [MIM:609741]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT22 includes nuclear cataract among others. Nuclear cataracts affect the central nucleus of the eye, and are often not highly visually significant. The density of the opacities varies greatly from fine dots to a dense, white and chalk-like, central cataract. The condition is usually bilateral. Nuclear cataracts are often combined with opacified cortical fibers encircling the nuclear opacity, which are referred to as cortical riders. {ECO:0000269|PubMed:15914629, ECO:0000269|PubMed:23508780}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.125

Intolerance Scores

• loftool: 0.808
• rvis_EVS: 0.82
• rvis_percentile_EVS: 87.99

Haploinsufficiency Scores

• pHI: 0.121
• hipred: N
• hipred_score: 0.284
• ghis: 0.483

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.376

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Crybb3
• Phenotype: skeleton phenotype

Gene ontology

• Biological process: visual perception
• Molecular function: structural constituent of eye lens;protein binding