BCR

BCR activator of RhoGEF and GTPase, the group of Pleckstrin homology domain containing|C2 domain containing|Dbl family Rho GEFs|My-T-BRC complex

Basic information

Region (hg38): 22:23179703-23318037

Previous symbols: [ "D22S11", "BCR1" ]

Links

ENSG00000186716 ∙ NCBI:613 ∙ OMIM:151410 ∙ HGNC:1014 ∙ Uniprot:P11274 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
CML treatment, response to	AD	Pharmacogenomic	Variants may confer resistance to certain medications (eg, dasatinib); Certain variants appear to confer STI571 resistance in CML treatment	General	11423618; 12654249; 14534339; 17684099

ClinVar

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

• not provided (56 variants)
• Inborn genetic diseases (49 variants)
• Chronic myelogenous leukemia, BCR-ABL1 positive (4 variants)
• Acute lymphoid leukemia;Chronic myelogenous leukemia, BCR-ABL1 positive (4 variants)
• not specified (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BCR 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			1	21	10	32
missense			52	5	5	62
nonsense						0
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				2	6	8
non coding				6		6
Total	0	0	55	32	15

Variants in BCR

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

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

Position	Type	Phenotype	Significance	ClinVar
22-23181068-G-T		not specified	Uncertain significance (Feb 26, 2024)
22-23181098-G-T			Benign (Dec 31, 2019)
22-23181122-C-T			Benign (Aug 17, 2018)
22-23181169-A-G		not specified	Uncertain significance (May 23, 2023)
22-23181174-C-T		not specified	Uncertain significance (Dec 17, 2023)
22-23181176-G-T			Likely benign (May 24, 2018)
22-23181192-C-T		not specified	Uncertain significance (Jan 03, 2022)
22-23181199-C-T		not specified	Uncertain significance (Sep 22, 2023)
22-23181220-C-G		not specified	Uncertain significance (Dec 17, 2021)
22-23181241-C-T		not specified	Uncertain significance (Jul 17, 2023)
22-23181270-G-A		not specified	Uncertain significance (Aug 03, 2022)
22-23181304-C-T		not specified	Uncertain significance (May 03, 2023)
22-23181353-C-A			Likely benign (Jul 01, 2022)
22-23181355-G-C			Likely benign (Apr 10, 2018)
22-23181355-G-T		not specified	Uncertain significance (Dec 28, 2022)
22-23181414-G-A		not specified	Uncertain significance (Sep 07, 2022)
22-23181415-C-T			Benign (Feb 01, 2024)
22-23181457-G-A			Benign (Aug 08, 2018)
22-23181460-A-C		not specified	Uncertain significance (Feb 05, 2024)
22-23181512-C-A		not specified	Uncertain significance (Nov 14, 2023)
22-23181524-G-A			Likely benign (Jul 17, 2018)
22-23181537-G-A		not specified	Uncertain significance (Jul 25, 2023)
22-23181541-A-G		not specified	Uncertain significance (Nov 03, 2022)
22-23181566-C-T		Acute lymphoid leukemia;Chronic myelogenous leukemia, BCR-ABL1 positive	Benign/Likely benign (Apr 05, 2022)
22-23181588-A-T		not specified	Uncertain significance (Dec 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BCR	protein_coding	protein_coding	ENST00000305877	23	138334

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.988	0.0124	125726	0	18	125744	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.888	685	754	0.909	0.0000469	8218
Missense in Polyphen		120	179.41	0.66884		1860
Synonymous	-1.91	370	326	1.13	0.0000221	2449
Loss of Function	5.79	10	57.4	0.174	0.00000263	679

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000518	0.000460
Ashkenazi Jewish	0.000202	0.000198
East Asian	0.00	0.00
Finnish	0.0000865	0.0000462
European (Non-Finnish)	0.0000449	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. Displays serine/threonine kinase activity. {ECO:0000269|PubMed:1657398, ECO:0000269|PubMed:1903516}.
• Disease: DISEASE: Leukemia, chronic myeloid (CML) [MIM:608232]: A clonal myeloproliferative disorder of a pluripotent stem cell with a specific cytogenetic abnormality, the Philadelphia chromosome (Ph), involving myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T-lymphoid cells, but not marrow fibroblasts. {ECO:0000269|PubMed:2407300, ECO:0000269|PubMed:3107980, ECO:0000269|PubMed:3540951}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Note=A chromosomal aberration involving BCR has been found in patients with chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with ABL1. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). {ECO:0000269|PubMed:3107980, ECO:0000269|PubMed:7665185}.
• Pathway: Chronic myeloid leukemia - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Imatinib Pathway, Pharmacokinetics/Pharmacodynamics;Imatinib and Chronic Myeloid Leukemia;Disease;Signal Transduction;inhibition of cellular proliferation by gleevec;integrin signaling pathway;bcr signaling pathway;ctcf: first multivalent nuclear factor;Rho GTPase cycle;Signaling by Rho GTPases;Regulation of RAC1 activity;Signaling by FGFR in disease;Signaling by cytosolic FGFR1 fusion mutants;FGFR1 mutant receptor activation;Signaling by FGFR1 in disease;Diseases of signal transduction;Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.764

Intolerance Scores

• loftool: 0.144
• rvis_EVS: -1.25
• rvis_percentile_EVS: 5.36

Haploinsufficiency Scores

• pHI: 0.279
• hipred: Y
• hipred_score: 0.816
• ghis: 0.515

Essentials

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

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Bcr
• 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); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; immune system phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; normal 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); hematopoietic system phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: negative regulation of cellular extravasation;renal system process;protein phosphorylation;signal transduction;brain development;peptidyl-tyrosine phosphorylation;actin cytoskeleton organization;regulation of Rho protein signal transduction;intracellular signal transduction;inner ear morphogenesis;regulation of vascular permeability;negative regulation of neutrophil degranulation;positive regulation of GTPase activity;protein autophosphorylation;platelet-derived growth factor receptor signaling pathway;homeostasis of number of cells;negative regulation of inflammatory response;positive regulation of phagocytosis;modulation of chemical synaptic transmission;neuromuscular process controlling balance;regulation of small GTPase mediated signal transduction;regulation of nitrogen compound metabolic process;regulation of cell cycle;definitive hemopoiesis;negative regulation of respiratory burst;negative regulation of blood vessel remodeling;intracellular protein transmembrane transport;cellular response to lipopolysaccharide;negative regulation of reactive oxygen species metabolic process
• Cellular component: cytosol;postsynaptic density;membrane;cell junction;protein-containing complex;postsynaptic membrane;extracellular exosome;Schaffer collateral - CA1 synapse;glutamatergic synapse;postsynaptic density, intracellular component
• Molecular function: protein serine/threonine kinase activity;protein tyrosine kinase activity;Rho guanyl-nucleotide exchange factor activity;GTPase activator activity;protein binding;ATP binding;kinase activity