6-156778889-CGGAGGAGGAGGAGGA-CGGAGGAGGAGGA

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.1232_1234delGAG(p.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 0.00451 in 1,314,634 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0048 ( 2 hom. )

Consequence

ARID1B
NM_001374828.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.98

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

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 6-156778889-CGGA-C is Benign according to our data. Variant chr6-156778889-CGGA-C is described in ClinVar as [Benign]. Clinvar id is 434373.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 = 0.00191 (273/142970) while in subpopulation EAS AF = 0.00298 (14/4694). AF 95% confidence interval is 0.0018. There are 0 homozygotes in GnomAd4. There are 157 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High AC in GnomAd4 at 273 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1 link	c.1232_1234delGAG	p.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
ARID1B	ENST00000636930.2 link	c.1232_1234delGAG	p.Gly411del	disruptive_inframe_deletion	Exon 1 of 20	2	NM_001374828.1	ENSP00000490491.2		Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes

AF:

0.00190

AC:

272

AN:

142898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00241

Gnomad ASJ

AF:

0.000296

Gnomad EAS

AF:

0.00297

Gnomad SAS

AF:

0.00224

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000927

Gnomad OTH

AF:

0.00102

GnomAD2 exomes

AF:

0.0140

AC:

468

AN:

33354

AF XY:

0.0150

show subpopulations

Gnomad AFR exome

AF:

0.0104

Gnomad AMR exome

AF:

0.0109

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.0240

Gnomad FIN exome

AF:

0.0173

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.0197

GnomAD4 exome

AF:

0.00483

AC:

5660

AN:

1171664

Hom.:

AF XY:

0.00533

AC XY:

3053

AN XY:

573152

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00414

AC:

AN:

22682

American (AMR)

AF:

0.00695

AC:

AN:

13814

Ashkenazi Jewish (ASJ)

AF:

0.00616

AC:

106

AN:

17214

East Asian (EAS)

AF:

0.00339

AC:

AN:

25362

South Asian (SAS)

AF:

0.0122

AC:

617

AN:

50426

European-Finnish (FIN)

AF:

0.0160

AC:

606

AN:

37926

Middle Eastern (MID)

AF:

0.00638

AC:

AN:

4234

European-Non Finnish (NFE)

AF:

0.00394

AC:

3757

AN:

953270

Other (OTH)

AF:

0.00580

AC:

271

AN:

46736

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.327

Heterozygous variant carriers

555

1110

1665

2220

2775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00191

AC:

273

AN:

142970

Hom.:

Cov.:

AF XY:

0.00225

AC XY:

157

AN XY:

69736

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

38928

American (AMR)

AF:

0.00241

AC:

AN:

14546

Ashkenazi Jewish (ASJ)

AF:

0.000296

AC:

AN:

3374

East Asian (EAS)

AF:

0.00298

AC:

AN:

4694

South Asian (SAS)

AF:

0.00225

AC:

AN:

4448

European-Finnish (FIN)

AF:

0.0121

AC:

111

AN:

9208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.000927

AC:

AN:

64692

Other (OTH)

AF:

0.00101

AC:

AN:

1982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00625

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jun 01, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ARID1B: BS1, BS2 -

not specified

Benign:2

Nov 08, 2016

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

ARID1B-related disorder

Benign:1

Mar 14, 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

Jul 14, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.0

Mutation Taster

=78/22

polymorphism

(source)

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

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6-156778889-CGGAGGAGGAGGAGGA-CGGAGGAGGAGGA

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