NM_001374828.1:c.1223_1234delGAGGAGGAGGAG

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_001374828.1(ARID1B):​c.1223_1234delGAGGAGGAGGAG​(p.Gly408_Gly411del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000776 in 1,366,606 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

ARID1B
NM_001374828.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:5

Conservation

PhyloP100: 3.18

Publications

0 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 -17 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_001374828.1
BP6
Variant 6-156778889-CGGAGGAGGAGGA-C is Benign according to our data. Variant chr6-156778889-CGGAGGAGGAGGA-C is described in ClinVar as [Likely_benign]. Clinvar id is 591999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000168 (24/143056) while in subpopulation EAS AF = 0.00298 (14/4694). AF 95% confidence interval is 0.0018. There are 0 homozygotes in GnomAd4. There are 10 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
BS2
High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARID1BNM_001374828.1 linkc.1223_1234delGAGGAGGAGGAG p.Gly408_Gly411del disruptive_inframe_deletion 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.1223_1234delGAGGAGGAGGAG p.Gly408_Gly411del disruptive_inframe_deletion Exon 1 of 20 2 NM_001374828.1 ENSP00000490491.2 Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes
AF:
0.000161
AC:
23
AN:
142982
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.000103
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00297
Gnomad SAS
AF:
0.000224
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000618
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000670
AC:
82
AN:
1223550
Hom.:
0
AF XY:
0.0000634
AC XY:
38
AN XY:
599380
show subpopulations
African (AFR)
AF:
0.000292
AC:
7
AN:
23958
American (AMR)
AF:
0.0000687
AC:
1
AN:
14566
Ashkenazi Jewish (ASJ)
AF:
0.0000537
AC:
1
AN:
18616
East Asian (EAS)
AF:
0.000924
AC:
25
AN:
27060
South Asian (SAS)
AF:
0.000114
AC:
6
AN:
52790
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40134
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4406
European-Non Finnish (NFE)
AF:
0.0000373
AC:
37
AN:
992596
Other (OTH)
AF:
0.000101
AC:
5
AN:
49424
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.470
Heterozygous variant carriers
0
5
10
14
19
24
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:
0.000168
AC:
24
AN:
143056
Hom.:
0
Cov.:
29
AF XY:
0.000143
AC XY:
10
AN XY:
69794
show subpopulations
African (AFR)
AF:
0.000128
AC:
5
AN:
38934
American (AMR)
AF:
0.00
AC:
0
AN:
14550
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3376
East Asian (EAS)
AF:
0.00298
AC:
14
AN:
4694
South Asian (SAS)
AF:
0.000225
AC:
1
AN:
4448
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
9258
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
254
European-Non Finnish (NFE)
AF:
0.0000618
AC:
4
AN:
64716
Other (OTH)
AF:
0.00
AC:
0
AN:
1982
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.510
Heterozygous variant carriers
0
1
3
4
6
7
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:
0.0000862
Hom.:
1

ClinVar

Significance: Benign/Likely benign
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:3
Jan 28, 2022
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Sep 16, 2018
Gharavi Laboratory, Columbia University
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:research

- -

Jan 13, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Sep 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

ARID1B: BS1, BS2 -

Inborn genetic diseases Benign:1
Aug 30, 2017
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

ARID1B-related disorder Benign:1
Aug 17, 2023
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
PhyloP100
3.2
Mutation Taster
=194/6
polymorphism

Splicing

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

Publications

Other links and lift over

dbSNP: rs747790383; hg19: chr6-157100023; API