ClinVar Genomic variation as it relates to human health
NM_001374828.1(ARID1B):c.4479G>A (p.Pro1493=)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001374828.1(ARID1B):c.4479G>A (p.Pro1493=)
Variation ID: 210291 Accession: VCV000210291.25
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6q25.3 6: 157198907 (GRCh38) [ NCBI UCSC ] 6: 157520041 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 5, 2015 May 1, 2024 Mar 12, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001374828.1:c.4479G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001361757.1:p.Pro1493= synonymous NM_001363725.2:c.1980G>A NP_001350654.1:p.Pro660= synonymous NM_001371656.1:c.4359G>A NP_001358585.1:p.Pro1453= synonymous NM_001374820.1:c.4359G>A NP_001361749.1:p.Pro1453= synonymous NM_017519.3:c.4320G>A NP_059989.3:p.Pro1440= synonymous NM_020732.3:c.4110G>A NP_065783.3:p.Pro1370= synonymous NC_000006.12:g.157198907G>A NC_000006.11:g.157520041G>A NG_066624.1:g.427882G>A - Protein change
- Other names
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- Canonical SPDI
- NC_000006.12:157198906:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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ARID1B | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1785 | 2116 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Sep 7, 2022 | RCV000657879.7 | |
no classifications from unflagged records (1) |
no classifications from unflagged records
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Jan 25, 2024 | RCV000415059.4 | |
Pathogenic/Likely pathogenic (7) |
criteria provided, multiple submitters, no conflicts
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May 4, 2022 | RCV000416951.12 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 12, 2024 | RCV001266859.5 | |
Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 10, 2021 | RCV001420197.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 10, 2021 | RCV001533021.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 20, 2023 | RCV003417699.4 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Dec 22, 2014)
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criteria provided, single submitter
Method: clinical testing
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Mental retardation, autosomal dominant 12
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000246523.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
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Pathogenic
(Jan 12, 2017)
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criteria provided, single submitter
Method: research
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Coffin-Siris syndrome 1
Affected status: yes
Allele origin:
de novo
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HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: CSER-HudsonAlpha
Accession: SCV000494583.3 First in ClinVar: Feb 12, 2017 Last updated: Feb 12, 2017 |
Number of individuals with the variant: 1
Clinical Features:
Agenesis of corpus callosum (present) , Delayed speech and language development (present) , Enlarged cisterna magna (present) , Colpocephaly (present)
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Pathogenic
(Aug 27, 2019)
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criteria provided, single submitter
Method: clinical testing
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Coffin-siris syndrome 1
Affected status: unknown
Allele origin:
germline
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Knight Diagnostic Laboratories, Oregon Health and Sciences University
Accession: SCV001448924.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 1
Clinical Features:
Global developmental delay (present) , Intellectual disability (present) , Sensorineural hearing loss (present) , Generalized hypotonia (present) , Tethered cord (present) , Delayed speech and … (more)
Global developmental delay (present) , Intellectual disability (present) , Sensorineural hearing loss (present) , Generalized hypotonia (present) , Tethered cord (present) , Delayed speech and language development (present) , Expressive language delay (present) , Short stature (present) , Obesity (present) , Relative macrocephaly (present) , Wide mouth (present) , Dysphagia (present) , Abnormality of the outer ear (present) , Posteriorly rotated ears (present) , Upslanted palpebral fissure (present) , Ptosis (present) , Myopia (disease) (present) , Strabismus (present) , Marcus Gunn pupil (present) , Abnormal thrombosis (present) , Abnormality of the menstrual cycle (present) , Absent speech (present) , Abnormality of the middle ear ossicles (present) (less)
Sex: female
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Pathogenic
(May 05, 2020)
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criteria provided, single submitter
Method: clinical testing
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Coffin-Siris syndrome 1
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001523088.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. [PMID 22405089, 27474218, 29286531, 28323383]
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Likely pathogenic
(Apr 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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See cases
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Genetics Laboratory, UDIAT-Centre Diagnòstic, Hospital Universitari Parc Tauli
Accession: SCV001622617.1
First in ClinVar: May 20, 2021 Last updated: May 20, 2021 |
Comment:
PVS1_strong;PM2_supporting;PM6_moderate
Clinical Features:
Intellectual disability (present) , Scoliosis (present) , Motor delay (present) , Delayed speech and language development (present) , Hyperactivity (present) , Abnormal facial shape (present) … (more)
Intellectual disability (present) , Scoliosis (present) , Motor delay (present) , Delayed speech and language development (present) , Hyperactivity (present) , Abnormal facial shape (present) , Connective tissue nevi (present) , Facial asymmetry (present) , Hypermelanotic macule (present) , Sandal gap (present) , Gynecomastia (present) (less)
Sex: male
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Pathogenic
(Jun 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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ARID1B-related BAFopathy
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001748840.1
First in ClinVar: Jul 10, 2021 Last updated: Jul 10, 2021 |
Observation 1: Observation 2: |
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Pathogenic
(Sep 07, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000779641.3
First in ClinVar: Jul 09, 2018 Last updated: Mar 04, 2023 |
Comment:
Affects the splice donor site and induces skipping of exon 17 causing a frameshift leading to a premature Stop codon (p.Arg1338ArgfsX76) (Hoyer et al., 2012); … (more)
Affects the splice donor site and induces skipping of exon 17 causing a frameshift leading to a premature Stop codon (p.Arg1338ArgfsX76) (Hoyer et al., 2012); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30349098, 22405089, 28323383, 27474218, 29286531, 15057123, 31406558) (less)
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Pathogenic
(Mar 12, 2024)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV001445039.4
First in ClinVar: Nov 21, 2020 Last updated: May 01, 2024 |
Comment:
The c.4110G>A (p.P1370P) alteration is located in coding exon 17 of the ARID1B gene. This nucleotide substitution does not change the proline (P) at codon … (more)
The c.4110G>A (p.P1370P) alteration is located in coding exon 17 of the ARID1B gene. This nucleotide substitution does not change the proline (P) at codon 1370. However, this change occurs in the last base pair of coding exon 17, which makes it likely to have some effect on normal mRNA splicing. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported as a de novo occurrence in multiple unrelated individuals with CSS (Hoyer, 2012; Mignot, 2016; Zweier, 2017). This nucleotide position is highly conserved in available vertebrate species. RNA functional analysis demonstrated that the alteration leads to out-of-frame skipping of exon 17 (Hoyer, 2012). In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on the available evidence, this alteration is classified as pathogenic. (less)
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Likely pathogenic
(Jul 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Coffin-Siris syndrome 1
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002054319.1
First in ClinVar: Jan 12, 2022 Last updated: Jan 12, 2022 |
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Pathogenic
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Coffin-Siris syndrome 1
Affected status: unknown
Allele origin:
germline
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Mendelics
Accession: SCV002518514.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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Likely pathogenic
(Dec 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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see cases
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University Hospital Muenster
Accession: SCV002577861.1
First in ClinVar: Oct 08, 2022 Last updated: Oct 08, 2022 |
Comment:
ACMG categories: PS5,PM2,PP3
Number of individuals with the variant: 1
Clinical Features:
Sleep apnea (present) , Low-set ears (present) , Hypertelorism (present) , Hypotonia (present) , Abnormal heart morphology (present) , Hypoplasia of the corpus callosum (present)
Age: 0-9 years
Sex: female
Tissue: blood
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Pathogenic
(Apr 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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ARID1B-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004107837.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The ARID1B c.4110G>A variant is not predicted to result in an amino acid change (p.=). This variant is predicted to weaken the canonical splice donor … (more)
The ARID1B c.4110G>A variant is not predicted to result in an amino acid change (p.=). This variant is predicted to weaken the canonical splice donor site (Alamut Visual Plus v1.6.1). This variant has been reported in multiple individuals with Coffin-Siris syndrome and the majority of cases were found to be de novo (see for example, Hoyer et al. 2012. PubMed ID: 22405089; Mignot et al. 2016. PubMed ID: 27474218; Tumiene et al. 2018. PubMed ID: 29286531; van der Sluijs et al. 2019. PubMed ID: 30349098). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating it is rare or absent in the general population. cDNA analyses indicated that this variant causes skipping of exon 17 and a shift to the translation reading frame (p.Arg1338Argfs*76, Hoyer et al. 2012. PubMed ID: 22405089) This variant is interpreted as pathogenic. (less)
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Pathogenic
(Aug 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003439486.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This variant has been observed in individual(s) with clinical features of Coffin-Siris syndrome and/or Coffin-Siris syndrome (PMID: 22405089, 27474218, 28323383). In at least one individual … (more)
This variant has been observed in individual(s) with clinical features of Coffin-Siris syndrome and/or Coffin-Siris syndrome (PMID: 22405089, 27474218, 28323383). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 1370 of the ARID1B mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ARID1B protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. ClinVar contains an entry for this variant (Variation ID: 210291). For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 17 and introduces a premature termination codon (PMID: 22405089). The resulting mRNA is expected to undergo nonsense-mediated decay. (less)
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Pathogenic
(Mar 09, 2012)
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no assertion criteria provided
Method: literature only
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COFFIN-SIRIS SYNDROME 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000902412.1
First in ClinVar: May 12, 2019 Last updated: May 12, 2019 |
Comment on evidence:
In a 19-year-old Finnish woman (P3) with Coffin-Siris syndrome-1 (CSS1; 135900), Zweier et al. (2017) identified a de novo heterozygous c.4110G-A transition (c.4110G-A, NM_020732.3) in … (more)
In a 19-year-old Finnish woman (P3) with Coffin-Siris syndrome-1 (CSS1; 135900), Zweier et al. (2017) identified a de novo heterozygous c.4110G-A transition (c.4110G-A, NM_020732.3) in the last coding basepair of exon 17 of the ARID1B gene, which was predicted to result in a synonymous substitution, but was located in a conserved splice donor site. The mutation, which was found by trio-based exome sequencing of the patient and her parents, was confirmed by Sanger sequencing. Functional studies of the variant and studies of patient cells were not performed, but Zweier et al. (2017) noted that the mutation had previously been reported by Hoyer et al. (2012), who had demonstrated that it causes the skipping of exon 17. Thus, the c.4110G-A transition was predicted to cause a frameshift and premature termination (His1339IlefsTer77), and was likely subject to nonsense-mediated mRNA decay. The patient had previously been reported by Poyhonen et al. (2004) as having a different disorder, but the findings of Zweier et al. (2017) confirmed the diagnosis of CSS1. (less)
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Uncertain significance
(Dec 29, 2015)
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Flagged submission
flagged submission
Method: clinical testing
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
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Constipation
Decreased body weight Failure to thrive Microcephaly Recurrent respiratory infections Seizure Short stature
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000492573.1
First in ClinVar: Jan 13, 2017 Last updated: Jan 13, 2017 |
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Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more |
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice. | Tumienė B | Clinical genetics | 2018 | PMID: 29286531 |
The HHID syndrome of hypertrichosis, hyperkeratosis, abnormal corpus callosum, intellectual disability, and minor anomalies is caused by mutations in ARID1B. | Zweier M | American journal of medical genetics. Part A | 2017 | PMID: 28323383 |
ARID1B mutations are the major genetic cause of corpus callosum anomalies in patients with intellectual disability. | Mignot C | Brain : a journal of neurology | 2016 | PMID: 27474218 |
Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability. | Hoyer J | American journal of human genetics | 2012 | PMID: 22405089 |
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
Hypertrichosis, hyperkeratosis, abnormal corpus callosum, mental retardation and dysmorphic features in three unrelated females. | Pöyhönen MH | Clinical dysmorphology | 2004 | PMID: 15057123 |
Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
Text-mined citations for rs797045277 ...
HelpRecord last updated May 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.