rs146598030

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_006015.6(ARID1A):​c.3408G>A​(p.Ala1136Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000447 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00046 ( 0 hom. )

Consequence

ARID1A
NM_006015.6 splice_region, synonymous

Scores

2
Splicing: ADA: 0.0001374
2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: -0.158
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 1-26772501-G-A is Benign according to our data. Variant chr1-26772501-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434322.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=1, Uncertain_significance=1}.
BS2
High AC in GnomAd4 at 43 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARID1ANM_006015.6 linkc.3408G>A p.Ala1136Ala splice_region_variant, synonymous_variant Exon 13 of 20 ENST00000324856.13 NP_006006.3 O14497-1
ARID1ANM_139135.4 linkc.3408G>A p.Ala1136Ala splice_region_variant, synonymous_variant Exon 13 of 20 NP_624361.1 O14497-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARID1AENST00000324856.13 linkc.3408G>A p.Ala1136Ala splice_region_variant, synonymous_variant Exon 13 of 20 1 NM_006015.6 ENSP00000320485.7 O14497-1

Frequencies

GnomAD3 genomes
AF:
0.000283
AC:
43
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000544
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000207
AC:
52
AN:
251334
Hom.:
0
AF XY:
0.000250
AC XY:
34
AN XY:
135824
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000405
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000464
AC:
678
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.000428
AC XY:
311
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.000575
Gnomad4 OTH exome
AF:
0.000447
GnomAD4 genome
AF:
0.000283
AC:
43
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.000269
AC XY:
20
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000544
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000369
Hom.:
0
Bravo
AF:
0.000193
EpiCase
AF:
0.000872
EpiControl
AF:
0.000771

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Benign:2
Feb 03, 2020
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Feb 04, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Intellectual disability, autosomal dominant 14 Uncertain:1
Oct 31, 2018
Fulgent Genetics, Fulgent Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:1
Nov 03, 2017
Genetic Services Laboratory, University of Chicago
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

ARID1A-related disorder Benign:1
Oct 07, 2021
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
20
DANN
Benign
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00014
dbscSNV1_RF
Benign
0.0040
SpliceAI score (max)
0.99
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.99
Position offset: 2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146598030; hg19: chr1-27098992; COSMIC: COSV61377294; COSMIC: COSV61377294; API