rs1276300860

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001374828.1(ARID1B):ā€‹c.1000T>Gā€‹(p.Cys334Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000227 in 1,500,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C334R) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000014 ( 0 hom., cov: 30)
Exomes š‘“: 0.000024 ( 0 hom. )

Consequence

ARID1B
NM_001374828.1 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.22624573).
BS2
High AC in GnomAdExome4 at 32 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ARID1BNM_001374828.1 linkuse as main transcriptc.1000T>G p.Cys334Gly missense_variant 1/20 ENST00000636930.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARID1BENST00000636930.2 linkuse as main transcriptc.1000T>G p.Cys334Gly missense_variant 1/202 NM_001374828.1 A2Q8NFD5-3

Frequencies

GnomAD3 genomes
AF:
0.0000136
AC:
2
AN:
146718
Hom.:
0
Cov.:
30
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:
0.0000302
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000236
AC:
32
AN:
1354090
Hom.:
0
Cov.:
37
AF XY:
0.0000194
AC XY:
13
AN XY:
668630
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000303
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000136
AC:
2
AN:
146718
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
71594
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000302
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Astrocytoma Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLaboratory of Molecular Neuropathology, The University of Texas Health Science Center at Houston-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
18
DANN
Benign
0.77
DEOGEN2
Benign
0.027
.;T;.;.
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.73
T;T;T;T
M_CAP
Pathogenic
0.85
D
MetaRNN
Benign
0.23
T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.1
.;L;L;L
MutationTaster
Benign
0.75
N;N;N;N
PrimateAI
Pathogenic
0.93
D
PROVEAN
Benign
-1.3
.;N;.;.
REVEL
Benign
0.034
Sift
Uncertain
0.020
.;D;.;.
Sift4G
Benign
0.21
.;T;.;.
Polyphen
0.0010, 0.0020
.;B;.;B
Vest4
0.21
MutPred
0.35
.;Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP
0.068
MPC
0.36
ClinPred
0.23
T
GERP RS
1.5
Varity_R
0.23
gMVP
0.22

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

LitVar

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

Other links and lift over

dbSNP: rs1276300860; hg19: chr6-157099814; API