Human Gene Module / Chromosome 8 / CHRNB3

CHRNB3cholinergic receptor nicotinic beta 3 subunit

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
4 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
8p11.21
Associated Disorders
-
Relevance to Autism

Two novel overlapping CNVs involving the CHRNB3 gene were identified in unrelated ASD cases in Prasad et al., 2012; however, these CNVs resided within an intronic region of the gene, no comparison with controls was reported, and segregation of the CNV with ASD was incomplete (i.e., not all affected siblings were positive for the CNV).

Molecular Function

The CHRNB3 gene encodes for a member of a superfamily of ligand-gated ion channels (the nicotinic acetylcholine receptors, or nAChRs) that mediate fast signal transmission at synapses.

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Reports related to CHRNB3 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
2 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
3 Support Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort Wu H , et al. (2019) Yes Macrocephaly
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Familial Maternal Multiplex 23275889 Prasad A , et al. (2013)
- - copy_number_loss Unknown Not maternal Multiplex 23275889 Prasad A , et al. (2013)
c.52+1G>A - splice_site_variant Familial Paternal Simplex 31674007 Wu H , et al. (2019)
c.1249C>T p.Gln417Ter stop_gained Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two novel overlapping CNVs involving the CHRNB3 gene were identified in unrelated ASD cases in Prasad et al., 2012; however, these CNVs resided within an intronic region of the gene, no comparison with controls was reported, and segregation of the CNV with ASD was incomplete (i.e., not all affected siblings were positive for the CNV).

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

Two novel overlapping CNVs involving the CHRNB3 gene were identified in unrelated ASD cases in Prasad et al., 2012; however, these CNVs resided within an intronic region of the gene, no comparison with controls was reported, and segregation of the CNV with ASD was incomplete (i.e., not all affected siblings were positive for the CNV).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Two novel overlapping CNVs involving the CHRNB3 gene were identified in unrelated ASD cases in Prasad et al., 2012; however, these CNVs resided within an intronic region of the gene, no comparison with controls was reported, and segregation of the CNV with ASD was incomplete (i.e., not all affected siblings were positive for the CNV).

Reports Added
[Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.2019] [New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

Two novel overlapping CNVs involving the CHRNB3 gene were identified in unrelated ASD cases in Prasad et al., 2012; however, these CNVs resided within an intronic region of the gene, no comparison with controls was reported, and segregation of the CNV with ASD was incomplete (i.e., not all affected siblings were positive for the CNV).

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

Increased from to 4

Description

Two novel overlapping CNVs involving the CHRNB3 gene were identified in unrelated ASD cases in Prasad et al., 2012; however, these CNVs resided within an intronic region of the gene, no comparison with controls was reported, and segregation of the CNV with ASD was incomplete (i.e., not all affected siblings were positive for the CNV).

Krishnan Probability Score

Score 0.56778128448318

Ranking 1157/25841 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 0.0001318633195395

Ranking 12947/18225 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 0.91416170853925

Ranking 8122/18665 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 -0.21574702973772

Ranking 15754/20870 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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