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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

ENSG00000186716NCBI:613OMIM:151410HGNC:1014Uniprot:P11274AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
CML treatment, response toADPharmacogenomicVariants may confer resistance to certain medications (eg, dasatinib); Certain variants appear to confer STI571 resistance in CML treatmentGeneral11423618; 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
clinvar
21
clinvar
10
clinvar
32
missense
52
clinvar
5
clinvar
5
clinvar
62
nonsense
0
start loss
0
frameshift
1
clinvar
1
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
0
splice region
2
6
8
non coding
6
clinvar
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
22-23181098-G-T Benign (Dec 31, 2019)779478
22-23181122-C-T Benign (Aug 17, 2018)719837
22-23181169-A-G Inborn genetic diseases Uncertain significance (May 23, 2023)2523339
22-23181176-G-T Likely benign (May 24, 2018)746123
22-23181192-C-T Inborn genetic diseases Uncertain significance (Jan 03, 2022)2368133
22-23181220-C-G Inborn genetic diseases Uncertain significance (Dec 17, 2021)2408190
22-23181241-C-T Inborn genetic diseases Uncertain significance (Jul 17, 2023)2593737
22-23181270-G-A Inborn genetic diseases Uncertain significance (Aug 03, 2022)2305183
22-23181304-C-T Inborn genetic diseases Uncertain significance (May 03, 2023)2522204
22-23181353-C-A Likely benign (Jul 01, 2022)2652957
22-23181355-G-C Likely benign (Apr 10, 2018)725929
22-23181355-G-T Inborn genetic diseases Uncertain significance (Dec 28, 2022)2340905
22-23181414-G-A Inborn genetic diseases Uncertain significance (Sep 07, 2022)2406111
22-23181415-C-T Benign (Feb 01, 2024)708500
22-23181457-G-A Benign (Aug 08, 2018)720879
22-23181460-A-C Inborn genetic diseases Uncertain significance (Dec 15, 2021)2374757
22-23181524-G-A Likely benign (Jul 17, 2018)761223
22-23181537-G-A Inborn genetic diseases Uncertain significance (Jul 25, 2023)2595129
22-23181541-A-G Inborn genetic diseases Uncertain significance (Nov 03, 2022)2322127
22-23181566-C-T Acute lymphoid leukemia;Chronic myelogenous leukemia, BCR-ABL1 positive Benign/Likely benign (Apr 05, 2022)780633
22-23181645-C-T Chronic myelogenous leukemia, BCR-ABL1 positive;Acute lymphoid leukemia Uncertain significance (Mar 30, 2021)625895
22-23181653-C-T Likely benign (Jul 11, 2018)734525
22-23181674-C-T Likely benign (Jul 06, 2018)759154
22-23181704-C-T Likely benign (Aug 09, 2018)762892
22-23181717-C-T Inborn genetic diseases Uncertain significance (Feb 28, 2023)2490647

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
BCRprotein_codingprotein_codingENST00000305877 23138334
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9880.01241257260181257440.0000716
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.8886857540.9090.00004698218
Missense in Polyphen120179.410.668841860
Synonymous-1.913703261.130.00002212449
Loss of Function5.791057.40.1740.00000263679

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0005180.000460
Ashkenazi Jewish0.0002020.000198
East Asian0.000.00
Finnish0.00008650.0000462
European (Non-Finnish)0.00004490.0000440
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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