GeneBe

rs1333869920

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006015.6(ARID1A):​c.4G>A​(p.Ala2Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ARID1A
NM_006015.6 missense

Scores

4
2
12

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.50

Publications

3 publications found
Variant links:
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 syndrome
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
  • intellectual disability, autosomal dominant 14
    Inheritance: 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: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.4231024).

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

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ARID1A
NM_006015.6
MANE Select
c.4G>Ap.Ala2Thr
missense
Exon 1 of 20NP_006006.3
ARID1A
NM_139135.4
c.4G>Ap.Ala2Thr
missense
Exon 1 of 20NP_624361.1O14497-2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ARID1A
ENST00000324856.13
TSL:1 MANE Select
c.4G>Ap.Ala2Thr
missense
Exon 1 of 20ENSP00000320485.7O14497-1
ARID1A
ENST00000850904.1
c.4G>Ap.Ala2Thr
missense
Exon 1 of 20ENSP00000520984.1A0ABJ7H312
ARID1A
ENST00000457599.7
TSL:5
c.4G>Ap.Ala2Thr
missense
Exon 1 of 20ENSP00000387636.2O14497-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
11414
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1133926
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
549984
African (AFR)
AF:
0.00
AC:
0
AN:
22886
American (AMR)
AF:
0.00
AC:
0
AN:
10238
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
15142
East Asian (EAS)
AF:
0.00
AC:
0
AN:
25794
South Asian (SAS)
AF:
0.00
AC:
0
AN:
37558
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
23676
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3014
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
950692
Other (OTH)
AF:
0.00
AC:
0
AN:
44926
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, multiple submitters, no conflicts
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
2
-
not provided (2)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.90
BayesDel_addAF
Benign
-0.040
T
BayesDel_noAF
Benign
-0.30
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.10
T
Eigen
Benign
0.16
Eigen_PC
Benign
0.20
FATHMM_MKL
Benign
0.38
N
LIST_S2
Benign
0.58
T
M_CAP
Pathogenic
0.79
D
MetaRNN
Benign
0.42
T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
0.97
L
PhyloP100
2.5
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-0.64
N
REVEL
Benign
0.048
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.024
D
Polyphen
0.73
P
Vest4
0.30
MutPred
0.20
Loss of helix (P = 0.0123)
MVP
0.32
MPC
0.64
ClinPred
0.54
D
GERP RS
3.9
PromoterAI
-0.34
Neutral
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
3.0
Varity_R
0.41
gMVP
0.64
Mutation Taster
=73/27
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1333869920; hg19: chr1-27022898; API