Human Gene Module / Chromosome 20 / BCAS1

BCAS1breast carcinoma amplified sequence 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 5
Rare Variants / Common Variants
7 / 0
Aliases
BCAS1, AIBC1,  NABC1
Associated Syndromes
-
Chromosome Band
20q13.2
Associated Disorders
-
Relevance to Autism

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014).

Molecular Function

This gene is a candidate oncogene that resides in a region at 20q13 which is amplified in a variety of tumor types and associated with more aggressive tumor phenotypes. It is expressed in brain and prostate, and at lower levels in testis, intestine and colon, overexpressed in most breast cancer cell lines, and down-regulated in some colorectal tumors.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to BCAS1 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
2 Primary Integrated systems analysis reveals a molecular network underlying autism spectrum disorders Li J , et al. (2015) Yes -
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
4 Support Homozygous deletions implicate non-coding epigenetic marks in Autism spectrum disorder Schmitz-Abe K et al. (2020) Yes -
5 Support - Woodbury-Smith M et al. (2022) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - nonsynonymous_variant Unknown - Unknown 25549968 Li J , et al. (2015)
- - copy_number_loss Familial Both parents - 32820185 Schmitz-Abe K et al. (2020)
- - copy_number_loss Familial Both parents Simplex 32820185 Schmitz-Abe K et al. (2020)
c.1216G>A p.Gly406Ser missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1388T>C p.Leu463Pro missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.723+26T>C - missense_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
c.536del p.Gly179GlufsTer65 frameshift_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). Both of the non-synonymous variants in BCAS1 identified in this study were absent in 1000 Genomes (as of Jan/ Feb. 2013) and dbSNP and had GERP++ conservation scores > 1.5.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). Both of the non-synonymous variants in BCAS1 identified in this study were absent in 1000 Genomes (as of Jan/ Feb. 2013) and dbSNP and had GERP++ conservation scores > 1.5.

7/1/2020
3
icon
3

Decreased from 3 to 3

Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). Both of the non-synonymous variants in BCAS1 identified in this study were absent in 1000 Genomes (as of Jan/ Feb. 2013) and dbSNP and had GERP++ conservation scores > 1.5.

Reports Added
[Homozygous deletions implicate non-coding epigenetic marks in Autism spectrum disorder2020]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). Both of the non-synonymous variants in BCAS1 identified in this study were absent in 1000 Genomes (as of Jan/ Feb. 2013) and dbSNP and had GERP++ conservation scores > 1.5.

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). Both of the non-synonymous variants in BCAS1 identified in this study were absent in 1000 Genomes (as of Jan/ Feb. 2013) and dbSNP and had GERP++ conservation scores > 1.5.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2018
icon
4

Increased from to 4

Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). Both of the non-synonymous variants in BCAS1 identified in this study were absent in 1000 Genomes (as of Jan/ Feb. 2013) and dbSNP and had GERP++ conservation scores > 1.5.

Krishnan Probability Score

Score 0.49510666099974

Ranking 3209/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.013656995737347

Ranking 9763/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.93942610994571

Ranking 14206/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score -0.043156040174864

Ranking 10159/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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