rs797045262
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_006015.6(ARID1A):c.31_56delAGCAGCCTGGGCAACCCGCCGCCGCC(p.Ser11AlafsTer91) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000263 in 1,139,696 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000026 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ARID1A
NM_006015.6 frameshift
NM_006015.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.69
Publications
6 publications found
Genes affected
ARID1A (HGNC:11110): (AT-rich interaction domain 1A) This gene encodes a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. It possesses at least two conserved domains that could be important for its function. First, it has a DNA-binding domain that can specifically bind an AT-rich DNA sequence known to be recognized by a SNF/SWI complex at the beta-globin locus. Second, the C-terminus of the protein can stimulate glucocorticoid receptor-dependent transcriptional activation. It is thought that the protein encoded by this gene confers specificity to the SNF/SWI complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
ARID1A Gene-Disease associations (from GenCC):
- Coffin-Siris syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- intellectual disability, autosomal dominant 14Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 16 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 131 pathogenic variants in the truncated region.
PP5
Variant 1-26696421-CCCCGCCGCCGCCAGCAGCCTGGGCAA-C is Pathogenic according to our data. Variant chr1-26696421-CCCCGCCGCCGCCAGCAGCCTGGGCAA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 30292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_006015.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ARID1A | TSL:1 MANE Select | c.31_56delAGCAGCCTGGGCAACCCGCCGCCGCC | p.Ser11AlafsTer91 | frameshift | Exon 1 of 20 | ENSP00000320485.7 | O14497-1 | ||
| ARID1A | c.31_56delAGCAGCCTGGGCAACCCGCCGCCGCC | p.Ser11AlafsTer91 | frameshift | Exon 1 of 20 | ENSP00000520984.1 | A0ABJ7H312 | |||
| ARID1A | TSL:5 | c.31_56delAGCAGCCTGGGCAACCCGCCGCCGCC | p.Ser11AlafsTer91 | frameshift | Exon 1 of 20 | ENSP00000387636.2 | O14497-2 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 148154Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
0
AN:
148154
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000263 AC: 3AN: 1139696Hom.: 0 AF XY: 0.00000542 AC XY: 3AN XY: 553350 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
3
AN:
1139696
Hom.:
AF XY:
AC XY:
3
AN XY:
553350
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
23054
American (AMR)
AF:
AC:
0
AN:
11292
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
15664
East Asian (EAS)
AF:
AC:
0
AN:
25828
South Asian (SAS)
AF:
AC:
1
AN:
38820
European-Finnish (FIN)
AF:
AC:
0
AN:
23942
Middle Eastern (MID)
AF:
AC:
0
AN:
3056
European-Non Finnish (NFE)
AF:
AC:
1
AN:
952852
Other (OTH)
AF:
AC:
0
AN:
45188
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.242
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
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Age
GnomAD4 genome 0.00 AC: 0AN: 148250Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 72448
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
148250
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
72448
African (AFR)
AF:
AC:
0
AN:
40562
American (AMR)
AF:
AC:
0
AN:
15016
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3436
East Asian (EAS)
AF:
AC:
0
AN:
4920
South Asian (SAS)
AF:
AC:
0
AN:
4734
European-Finnish (FIN)
AF:
AC:
0
AN:
9790
Middle Eastern (MID)
AF:
AC:
0
AN:
278
European-Non Finnish (NFE)
AF:
AC:
0
AN:
66568
Other (OTH)
AF:
AC:
0
AN:
2054
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
3
-
-
Intellectual disability, autosomal dominant 14 (3)
2
-
-
not provided (2)
1
-
-
Coffin-Siris syndrome 1 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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