CRYBA1

crystallin beta A1, the group of Beta-gamma crystallins

Basic information

Region (hg38): 17:29246858-29254494

Previous symbols: [ "CRYB1" ]

Links

ENSG00000108255 ∙ NCBI:1411 ∙ OMIM:123610 ∙ HGNC:2394 ∙ Uniprot:P05813 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cataract 10 multiple types (Definitive), mode of inheritance: AD
• early-onset sutural cataract (Supportive), mode of inheritance: AD
• early-onset nuclear cataract (Supportive), mode of inheritance: AD
• early-onset posterior polar cataract (Supportive), mode of inheritance: AD
• early-onset lamellar cataract (Supportive), mode of inheritance: AD
• cataract 10 multiple types (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 10, multiple types	AD	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	7573044; 9788845; 17653060; 20142846; 21686330; 21850182; 21866213; 22665976

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CRYBA1 gene.

• Cataract 10 multiple types (36 variants)
• not provided (20 variants)
• Inborn genetic diseases (8 variants)
• not specified (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRYBA1 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				2	3	5
missense			12	3	2	17
nonsense			2			2
start loss						0
frameshift		2	3			5
inframe indel		2				2
splice donor/acceptor (+/-2bp)	3	2	1			6
splice region			1	4		5
non coding				6	7	13
Total	3	6	18	11	12

Highest pathogenic variant AF is 0.0000263

Variants in CRYBA1

This is a list of pathogenic ClinVar variants found in the CRYBA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-29246901-A-C			Likely benign (Oct 23, 2018)
17-29246901-A-G		Cataract 10 multiple types	Likely benign (Sep 30, 2019)
17-29249001-G-A			Benign (Aug 03, 2018)
17-29249162-A-G		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
17-29249184-C-T		not specified • Cataract 10 multiple types	Benign/Likely benign (Jan 18, 2024)
17-29249185-G-A		Cataract 10 multiple types • CRYBA1-related disorder	Benign/Likely benign (Jul 12, 2023)
17-29249199-C-T		Cataract 10 multiple types	Benign (Aug 18, 2022)
17-29249237-C-T			Likely benign (Jan 20, 2019)
17-29249281-T-G			Benign (Aug 03, 2018)
17-29249894-CA-C			Benign (Aug 03, 2018)
17-29249944-T-C			Benign (Jun 28, 2018)
17-29250162-G-A		Cataract 10 multiple types	Benign (Oct 13, 2023)
17-29250174-C-T		Cataract 10 multiple types	Benign/Likely benign (Dec 07, 2023)
17-29250186-C-T		Cataract 10 multiple types	Uncertain significance (Dec 07, 2023)
17-29250202-G-C		Inborn genetic diseases	Uncertain significance (Jun 26, 2023)
17-29250230-AC-A			Uncertain significance (Mar 29, 2019)
17-29250258-G-A		Cataract 10 multiple types • CRYBA1-related disorder	Likely benign (Oct 03, 2023)
17-29250266-G-C		Inborn genetic diseases	Uncertain significance (Jan 19, 2024)
17-29250276-G-A		Inborn genetic diseases	Uncertain significance (Nov 09, 2022)
17-29250282-T-G		Cataract 10 multiple types	Uncertain significance (Jun 20, 2022)
17-29250301-G-A		Cataract 10 multiple types • Inborn genetic diseases • CRYBA1-related disorder	Pathogenic (Dec 16, 2023)
17-29250301-G-C		Cataract 10 multiple types • CRYBA1-related disorder	Pathogenic (Dec 14, 2023)
17-29250301-G-T		Cataract 10 multiple types	Pathogenic (Mar 01, 2018)
17-29250305-G-A		Cataract 10 multiple types	Uncertain significance (Jul 29, 2023)
17-29250316-C-T		not specified • Cataract 10 multiple types	Benign (Jan 25, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRYBA1	protein_coding	protein_coding	ENST00000225387	6	7632

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000641	0.910	125716	0	32	125748	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.626	109	129	0.845	0.00000756	1436
Missense in Polyphen		34	43.922	0.7741		509
Synonymous	-0.563	48	43.3	1.11	0.00000248	356
Loss of Function	1.56	9	15.7	0.574	8.71e-7	157

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.000544	0.000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000114	0.000114
Middle Eastern	0.000544	0.000544
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Crystallins are the dominant structural components of the vertebrate eye lens.
• Disease: DISEASE: Cataract 10, multiple types (CTRCT10) [MIM:600881]: 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. CTRCT10 includes congenital zonular with sutural opacities, among others. This is a form of zonular cataract with an erect Y-shaped anterior and an inverted Y-shaped posterior sutural opacities. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Zonular cataracts generally do not involve the embryonic nucleus, though sometimes they involve the fetal nucleus. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes. {ECO:0000269|PubMed:15016766, ECO:0000269|PubMed:9788845}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.177

Intolerance Scores

• loftool: 0.768
• rvis_EVS: 0.44
• rvis_percentile_EVS: 77.7

Haploinsufficiency Scores

• pHI: 0.589
• hipred: N
• hipred_score: 0.319

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.210

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cryba1
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; pigmentation phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of cytokine production;lens development in camera-type eye;visual perception;negative regulation of phosphatidylinositol 3-kinase signaling;negative regulation of TOR signaling;negative regulation of protein kinase B signaling;negative regulation of ERK1 and ERK2 cascade;positive regulation of anoikis
• Cellular component: nucleus;cytoplasm
• Molecular function: molecular_function;structural constituent of eye lens;protein binding