6-156778268-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_001374828.1(ARID1B):c.606_611dupGCAGCA(p.Gln203_Gln204dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 1,536,714 control chromosomes in the GnomAD database, including 93 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q204dup) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.016 ( 63 hom., cov: 30)

Exomes 𝑓: 0.0021 ( 30 hom. )

Consequence

ARID1B
NM_001374828.1 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.64

Publications

5 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:

ENSG00000271551 (HGNC:):

ENSG00000271551 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 6-156778268-C-CCAGCAG is Benign according to our data. Variant chr6-156778268-C-CCAGCAG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374828.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARID1B	NM_001374828.1	MANE Select	c.606_611dupGCAGCA	p.Gln203_Gln204dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1
ARID1B	NM_001438482.1		c.606_611dupGCAGCA	p.Gln203_Gln204dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
ARID1B	NM_001438483.1		c.606_611dupGCAGCA	p.Gln203_Gln204dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425412.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.606_611dupGCAGCA	p.Gln203_Gln204dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2
ARID1B	ENST00000346085.10	TSL:1	c.606_611dupGCAGCA	p.Gln203_Gln204dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5
ARID1B	ENST00000350026.11	TSL:1	c.606_611dupGCAGCA	p.Gln203_Gln204dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2468

AN:

151248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00604

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000872

Gnomad OTH

AF:

0.0130

GnomAD2 exomes

AF:

0.00389

AC:

503

AN:

129416

AF XY:

0.00317

show subpopulations

Gnomad AFR exome

AF:

0.0535

Gnomad AMR exome

AF:

0.00380

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000532

Gnomad FIN exome

AF:

0.000103

Gnomad NFE exome

AF:

0.000856

Gnomad OTH exome

AF:

0.00290

GnomAD4 exome

AF:

0.00210

AC:

2911

AN:

1385352

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

1275

AN XY:

683512

show subpopulations

African (AFR)

AF:

0.0554

AC:

1735

AN:

31312

American (AMR)

AF:

0.00417

AC:

148

AN:

35516

Ashkenazi Jewish (ASJ)

AF:

0.0000798

AC:

AN:

25064

East Asian (EAS)

AF:

0.000310

AC:

AN:

35518

South Asian (SAS)

AF:

0.000483

AC:

AN:

78742

European-Finnish (FIN)

AF:

0.0000481

AC:

AN:

41554

Middle Eastern (MID)

AF:

0.00520

AC:

AN:

5578

European-Non Finnish (NFE)

AF:

0.000662

AC:

711

AN:

1074368

Other (OTH)

AF:

0.00407

AC:

235

AN:

57700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

131

262

393

524

655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.0163

AC:

2466

AN:

151362

Hom.:

Cov.:

AF XY:

0.0159

AC XY:

1173

AN XY:

73992

show subpopulations

African (AFR)

AF:

0.0554

AC:

2285

AN:

41280

American (AMR)

AF:

0.00603

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.000196

AC:

AN:

5104

South Asian (SAS)

AF:

0.00

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10520

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000872

AC:

AN:

67668

Other (OTH)

AF:

0.0129

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

110

220

330

440

550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00111

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Sep 30, 2015

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

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Coffin-Siris syndrome 1

Benign:2

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Sep 27, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Apr 14, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22405089)

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inborn genetic diseases

Benign:1

Jul 12, 2018

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 v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.6

Mutation Taster

=80/20

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over