NM_001374828.1:c.1238G>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001374828.1(ARID1B):​c.1238G>C​(p.Gly413Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000402 in 1,317,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

ARID1B
NM_001374828.1 missense

Scores

1
1
17

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: -0.368

Publications

1 publications found
Variant links:
Genes affected
ARID1B (HGNC:18040): (AT-rich interaction domain 1B) This locus encodes an AT-rich DNA interacting domain-containing protein. The encoded protein is a component of the SWI/SNF chromatin remodeling complex and may play a role in cell-cycle activation. The protein encoded by this locus is similar to AT-rich interactive domain-containing protein 1A. These two proteins function as alternative, mutually exclusive ARID-subunits of the SWI/SNF complex. The associated complexes play opposing roles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]
ARID1B Gene-Disease associations (from GenCC):
  • Coffin-Siris syndrome
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina, ClinGen
  • Coffin-Siris syndrome 1
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.15980974).
BP6
Variant 6-156778918-G-C is Benign according to our data. Variant chr6-156778918-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434376.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].
BS2
High AC in GnomAdExome4 at 51 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARID1BNM_001374828.1 linkc.1238G>C p.Gly413Ala missense_variant Exon 1 of 20 ENST00000636930.2 NP_001361757.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARID1BENST00000636930.2 linkc.1238G>C p.Gly413Ala missense_variant Exon 1 of 20 2 NM_001374828.1 ENSP00000490491.2 Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes
AF:
0.0000136
AC:
2
AN:
147162
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000301
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
12388
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
AF:
0.0000436
AC:
51
AN:
1169976
Hom.:
0
Cov.:
35
AF XY:
0.0000405
AC XY:
23
AN XY:
567354
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
23436
American (AMR)
AF:
0.00
AC:
0
AN:
9406
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
16010
East Asian (EAS)
AF:
0.00
AC:
0
AN:
24340
South Asian (SAS)
AF:
0.00
AC:
0
AN:
37236
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
34232
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3638
European-Non Finnish (NFE)
AF:
0.0000513
AC:
50
AN:
974294
Other (OTH)
AF:
0.0000211
AC:
1
AN:
47384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
3
7
10
14
17
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000136
AC:
2
AN:
147162
Hom.:
0
Cov.:
29
AF XY:
0.0000139
AC XY:
1
AN XY:
71782
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
40108
American (AMR)
AF:
0.00
AC:
0
AN:
14850
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3424
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4652
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4688
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
9862
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
282
European-Non Finnish (NFE)
AF:
0.0000301
AC:
2
AN:
66384
Other (OTH)
AF:
0.00
AC:
0
AN:
2022
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000712
Hom.:
0
ExAC
AF:
0.0000310
AC:
1

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:3
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Coffin-Siris syndrome 1 Uncertain:1Benign:1
Jul 15, 2021
Genome-Nilou Lab
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jul 02, 2020
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:research

- -

not provided Benign:2
Dec 04, 2020
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jun 28, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not specified Uncertain:1
Feb 03, 2017
Genetic Services Laboratory, University of Chicago
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
17
DANN
Benign
0.53
DEOGEN2
Benign
0.013
.;T;.;.
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.055
N
LIST_S2
Benign
0.48
T;T;T;T
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.16
T;T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
0.0
.;N;N;N
PhyloP100
-0.37
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-0.060
.;N;.;.
REVEL
Benign
0.047
Sift
Benign
0.068
.;T;.;.
Sift4G
Benign
0.55
.;T;.;.
Polyphen
0.95, 0.97
.;P;.;D
Vest4
0.16
MutPred
0.24
.;Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);
MVP
0.26
MPC
0.31
ClinPred
0.24
T
GERP RS
1.1
PromoterAI
0.020
Neutral
Varity_R
0.061
gMVP
0.27
Mutation Taster
=90/10
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: rs749315126; hg19: chr6-157100052; API