NM_001374828.1:c.1185_1193delCGGCGGCGG

Variant names:

Variant summary

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

The NM_001374828.1(ARID1B):c.1185_1193delCGGCGGCGG(p.Gly396_Gly398del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00199 in 1,403,448 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 3 hom., cov: 29)

Exomes 𝑓: 0.0019 ( 7 hom. )

Consequence

ARID1B
NM_001374828.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.68

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

ARID1B links:

ENSG00000296922 (HGNC:):

ENSG00000296922 links:

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 6-156778847-GGGCGGCGGC-G is Benign according to our data. Variant chr6-156778847-GGGCGGCGGC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 434371.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 = 0.00267 (395/147916) while in subpopulation EAS AF = 0.00637 (31/4864). AF 95% confidence interval is 0.00461. There are 3 homozygotes in GnomAd4. There are 213 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High AC in GnomAd4 at 395 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1 link	c.1185_1193delCGGCGGCGG	p.Gly396_Gly398del	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
ARID1B	ENST00000636930.2 link	c.1185_1193delCGGCGGCGG	p.Gly396_Gly398del	disruptive_inframe_deletion	Exon 1 of 20	2	NM_001374828.1	ENSP00000490491.2		Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes

AF:

0.00266

AC:

393

AN:

147812

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00343

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00147

Gnomad ASJ

AF:

0.000878

Gnomad EAS

AF:

0.00656

Gnomad SAS

AF:

0.00172

Gnomad FIN

AF:

0.00670

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00176

Gnomad OTH

AF:

0.00343

GnomAD2 exomes

AF:

0.00247

AC:

137

AN:

55508

AF XY:

0.00219

show subpopulations

Gnomad AFR exome

AF:

0.00198

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.000245

Gnomad EAS exome

AF:

0.00797

Gnomad FIN exome

AF:

0.00723

Gnomad NFE exome

AF:

0.00116

Gnomad OTH exome

AF:

0.00155

GnomAD4 exome

AF:

0.00191

AC:

2395

AN:

1255532

Hom.:

AF XY:

0.00188

AC XY:

1160

AN XY:

617146

show subpopulations

African (AFR)

AF:

0.00336

AC:

AN:

24704

American (AMR)

AF:

0.00135

AC:

AN:

17060

Ashkenazi Jewish (ASJ)

AF:

0.00122

AC:

AN:

20424

East Asian (EAS)

AF:

0.00732

AC:

202

AN:

27604

South Asian (SAS)

AF:

0.00133

AC:

AN:

58572

European-Finnish (FIN)

AF:

0.00888

AC:

377

AN:

42440

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5046

European-Non Finnish (NFE)

AF:

0.00146

AC:

1470

AN:

1008970

Other (OTH)

AF:

0.00256

AC:

130

AN:

50712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

111

222

332

443

554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.00267

AC:

395

AN:

147916

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

213

AN XY:

72274

show subpopulations

African (AFR)

AF:

0.00347

AC:

140

AN:

40310

American (AMR)

AF:

0.00147

AC:

AN:

15014

Ashkenazi Jewish (ASJ)

AF:

0.000878

AC:

AN:

3418

East Asian (EAS)

AF:

0.00637

AC:

AN:

4864

South Asian (SAS)

AF:

0.00172

AC:

AN:

4656

European-Finnish (FIN)

AF:

0.00670

AC:

AN:

9852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00176

AC:

117

AN:

66586

Other (OTH)

AF:

0.00388

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00115

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ARID1B: BS1, BS2 -

May 13, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Nov 16, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ARID1B-related disorder

Benign:1

Sep 24, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Inborn genetic diseases

Benign:1

Apr 05, 2024

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. -

Coffin-Siris syndrome 1

Benign:1

May 30, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.7

Mutation Taster

=184/16

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over