SMARCB1

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1, the group of Protein phosphatase 1 regulatory subunits|BAF complex|PBAF complex

Basic information

Region (hg38): 22:23786930-23838009

Previous symbols: [ "SNF5L1" ]

Links

ENSG00000099956 ∙ NCBI:6598 ∙ OMIM:601607 ∙ HGNC:11103 ∙ Uniprot:Q12824 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• rhabdoid tumor predisposition syndrome 1 (Definitive), mode of inheritance: AD
• rhabdoid tumor predisposition syndrome 1 (Strong), mode of inheritance: AD
• Coffin-Siris syndrome (Supportive), mode of inheritance: AD
• schwannomatosis (Supportive), mode of inheritance: AD
• familial rhabdoid tumor (Supportive), mode of inheritance: AD
• familial multiple meningioma (Supportive), mode of inheritance: AD
• rhabdoid tumor predisposition syndrome 1 (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 15 (Moderate), mode of inheritance: AD
• schwannomatosis 1 (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Limited), mode of inheritance: AD
• intellectual disability, autosomal dominant 15 (Strong), mode of inheritance: AD
• rhabdoid tumor predisposition syndrome 1 (Strong), mode of inheritance: AD
• rhabdoid tumor predisposition syndrome 1 (Definitive), mode of inheritance: AD
• Coffin-Siris syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Schwannomatosis 1; Rhabdoid tumor predisposition syndrome 1	AD	Oncologic	Surveillance/early treatment of tumors may reduce morbidity	Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Genitourinary	6091860; 2543225; 9737241; 10521299; 17357086; 18285426; 18072270; 19582488; 20930055; 22426308; 22038540

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMARCB1 gene.

• not provided (743 variants)
• Hereditary cancer-predisposing syndrome (328 variants)
• Rhabdoid tumor predisposition syndrome 1 (54 variants)
• Schwannomatosis 1 (42 variants)
• not specified (30 variants)
• Intellectual disability, autosomal dominant 15 (23 variants)
• Inborn genetic diseases (10 variants)
• Schwannomatosis (7 variants)
• Coffin-Siris syndrome (5 variants)
• SMARCB1-related condition (5 variants)
• SMARCB1-related BAFopathy (4 variants)
• Rhabdoid tumor predisposition syndrome (4 variants)
• Rhabdoid tumor predisposition syndrome 2 (2 variants)
• Autism spectrum disorder (2 variants)
• Rhabdoid tumor predisposition syndrome 1;Intellectual disability, autosomal dominant 15;Schwannomatosis 1 (1 variants)
• Neoplasm of the central nervous system (1 variants)
• Schwannoma;Peripheral schwannoma (1 variants)
• Developmental disorder (1 variants)
• Neurodevelopmental disorder (1 variants)
• See cases (1 variants)
• Ovarian cancer (1 variants)
• Intellectual disability (1 variants)
• SMARCB1-Related Disorders (1 variants)
• Teratoid tumor, atypical (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMARCB1 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	217	1	222
missense		8	281	1		290
nonsense	14					14
start loss			1	1		2
frameshift	21	1		1		23
inframe indel	1	1	10			12
splice donor/acceptor (+/-2bp)	4	14				18
splice region			22	39	3	64
non coding	2	1	30	121	56	210
Total	42	25	326	341	57

Variants in SMARCB1

This is a list of pathogenic ClinVar variants found in the SMARCB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-23786942-G-T			Benign (Jan 15, 2024)
22-23786986-G-A		Rhabdoid tumor predisposition syndrome 1 • Schwannomatosis 1	Benign/Likely benign (Apr 10, 2022)
22-23787013-G-A		Schwannomatosis 1 • Rhabdoid tumor predisposition syndrome 1	Uncertain significance (Jan 12, 2018)
22-23787021-C-T		Coffin-Siris syndrome • Schwannomatosis • Rhabdoid tumor predisposition syndrome	Uncertain significance (Jun 14, 2016)
22-23787022-T-C		Schwannomatosis 1 • Rhabdoid tumor predisposition syndrome 1	Uncertain significance (Jan 13, 2018)
22-23787053-C-T		Schwannomatosis 1 • Rhabdoid tumor predisposition syndrome 1	Benign (Jun 23, 2018)
22-23787055-C-T		Rhabdoid tumor predisposition syndrome 1 • Schwannomatosis 1	Benign/Likely benign (May 01, 2023)
22-23787063-A-G		Schwannomatosis 1 • Rhabdoid tumor predisposition syndrome 1	Uncertain significance (Jan 13, 2018)
22-23787087-C-T		Schwannomatosis 1 • Rhabdoid tumor predisposition syndrome 1	Uncertain significance (Jan 13, 2018)
22-23787139-C-T		Rhabdoid tumor predisposition syndrome 1 • Schwannomatosis 1	Benign/Likely benign (Jun 22, 2018)
22-23787153-C-T		Schwannomatosis 1 • Rhabdoid tumor predisposition syndrome 1	Benign (Jan 12, 2018)
22-23787159-C-G		not specified	Likely benign (Jun 01, 2017)
22-23787165-C-A		Hereditary cancer-predisposing syndrome	Uncertain significance (Sep 20, 2023)
22-23787166-C-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Dec 12, 2022)
22-23787167-G-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Feb 27, 2024)
22-23787168-CAAT-C			Uncertain significance (Dec 27, 2022)
22-23787169-A-C		Hereditary cancer-predisposing syndrome	Uncertain significance (Mar 07, 2023)
22-23787169-AATG-A		Rhabdoid tumor predisposition syndrome 1	Uncertain significance (May 10, 2023)
22-23787170-A-C			Uncertain significance (Nov 03, 2023)
22-23787170-A-G		not specified • Hereditary cancer-predisposing syndrome • Schwannomatosis 1 • Rhabdoid tumor predisposition syndrome 1	Benign/Likely benign (Jan 25, 2024)
22-23787173-A-G			Uncertain significance (Dec 04, 2021)
22-23787174-T-G			Uncertain significance (Sep 29, 2022)
22-23787175-G-A			Uncertain significance (May 20, 2023)
22-23787177-T-A			Uncertain significance (Jul 28, 2023)
22-23787178-GA-TT			Uncertain significance (Mar 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMARCB1	protein_coding	protein_coding	ENST00000263121	9	47554

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00290	125742	0	3	125745	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.60	74	227	0.327	0.0000145	2537
Missense in Polyphen		20	67.578	0.29595		718
Synonymous	-0.346	99	94.7	1.05	0.00000691	729
Loss of Function	4.10	1	21.6	0.0464	0.00000131	234

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Core component of the BAF (hSWI/SNF) complex. This ATP- dependent chromatin-remodeling complex plays important roles in cell proliferation and differentiation, in cellular antiviral activities and inhibition of tumor formation. The BAF complex is able to create a stable, altered form of chromatin that constrains fewer negative supercoils than normal. This change in supercoiling would be due to the conversion of up to one-half of the nucleosomes on polynucleosomal arrays into asymmetric structures, termed altosomes, each composed of 2 histones octamers. Stimulates in vitro the remodeling activity of SMARCA4/BRG1/BAF190A. Involved in activation of CSF1 promoter. Belongs to the neural progenitors- specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Plays a key role in cell-cycle control and causes cell cycle arrest in G0/G1. {ECO:0000250|UniProtKB:Q9Z0H3, ECO:0000269|PubMed:10078207, ECO:0000269|PubMed:12226744, ECO:0000269|PubMed:14604992, ECO:0000269|PubMed:16267391, ECO:0000269|PubMed:16314535, ECO:0000269|PubMed:9448295}.
• Disease: DISEASE: Rhabdoid tumor predisposition syndrome 1 (RTPS1) [MIM:609322]: A familial cancer syndrome predisposing to renal or extrarenal malignant rhabdoid tumors and to a variety of tumors of the central nervous system, including choroid plexus carcinoma, medulloblastoma, and central primitive neuroectodermal tumors. Rhabdoid tumors are the most aggressive and lethal malignancies occurring in early childhood. {ECO:0000269|PubMed:9671307, ECO:0000269|PubMed:9892189}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Schwannomatosis 1 (SWNTS1) [MIM:162091]: A cancer syndrome in which patients develop multiple non-vestibular schwannomas, benign neoplasms that arise from Schwann cells of the cranial, peripheral, and autonomic nerves. {ECO:0000269|PubMed:17357086, ECO:0000269|PubMed:18072270}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Coffin-Siris syndrome 3 (CSS3) [MIM:614608]: A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. Both autosomal dominant and autosomal recessive inheritance patterns have been reported. {ECO:0000269|PubMed:22426308, ECO:0000269|PubMed:22726846, ECO:0000269|PubMed:23906836}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thermogenesis - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Tumor suppressor activity of SMARCB1;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;the information processing pathway at the ifn beta enhancer;Generic Transcription Pathway;RNA Polymerase II Transcription;RMTs methylate histone arginines;Chromatin modifying enzymes;Chromatin organization;chromatin remodeling by hswi/snf atp-dependent complexes;TNFalpha;Transcriptional regulation by RUNX1;Validated nuclear estrogen receptor beta network;Regulation of retinoblastoma protein (Consensus)

Recessive Scores

• pRec: 0.298

Intolerance Scores

• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.832
• hipred: Y
• hipred_score: 0.816
• ghis: 0.694

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smarcb1
• Phenotype: digestive/alimentary 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); vision/eye phenotype; immune system phenotype; embryo phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: RNA polymerase I preinitiation complex assembly;nucleosome disassembly;chromatin remodeling;regulation of transcription by RNA polymerase II;cell cycle;nervous system development;DNA integration;single stranded viral RNA replication via double stranded DNA intermediate;ATP-dependent chromatin remodeling;positive regulation by host of viral transcription;positive regulation of transcription by RNA polymerase II;positive regulation of DNA-binding transcription factor activity;positive regulation of histone H4 acetylation;negative regulation of histone H3-K9 dimethylation;negative regulation of histone H3-K9 trimethylation;positive regulation of transcription of nucleolar large rRNA by RNA polymerase I;positive regulation of glucose mediated signaling pathway;positive regulation of histone H3-K9 acetylation;regulation of histone H4-K16 acetylation
• Cellular component: nuclear chromatin;fibrillar center;nucleus;nucleoplasm;nucleolus;SWI/SNF complex;protein-containing complex;brahma complex;intracellular membrane-bounded organelle;npBAF complex;nBAF complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;RNA polymerase I CORE element sequence-specific DNA binding;p53 binding;DNA binding;transcription coactivator activity;protein binding;Tat protein binding;nucleosomal DNA binding