6-156778847-GGGCGGCGGCGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGCGGCGGC

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.1191_1193dupCGG(p.Gly398dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00216 in 1,403,452 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G398G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0067 ( 6 hom., cov: 29)

Exomes 𝑓: 0.0016 ( 14 hom. )

Consequence

ARID1B
NM_001374828.1 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

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-G-GGGC is Benign according to our data. Variant chr6-156778847-G-GGGC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0067 (991/147922) while in subpopulation AFR AF = 0.02 (807/40308). AF 95% confidence interval is 0.0189. There are 6 homozygotes in GnomAd4. There are 484 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High AC in GnomAd4 at 991 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1 link	c.1191_1193dupCGG	p.Gly398dup	disruptive_inframe_insertion	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.1191_1193dupCGG	p.Gly398dup	disruptive_inframe_insertion	Exon 1 of 20	2	NM_001374828.1	ENSP00000490491.2		Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes

AF:

0.00671

AC:

992

AN:

147818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00292

Gnomad EAS

AF:

0.00205

Gnomad SAS

AF:

0.00322

Gnomad FIN

AF:

0.000710

Gnomad MID

AF:

0.00333

Gnomad NFE

AF:

0.00120

Gnomad OTH

AF:

0.00588

GnomAD2 exomes

AF:

0.00104

AC:

AN:

55508

AF XY:

0.00107

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00122

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000563

Gnomad NFE exome

AF:

0.000634

Gnomad OTH exome

AF:

0.00155

GnomAD4 exome

AF:

0.00163

AC:

2043

AN:

1255530

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

993

AN XY:

617140

show subpopulations

African (AFR)

AF:

0.0243

AC:

601

AN:

24688

American (AMR)

AF:

0.00387

AC:

AN:

17064

Ashkenazi Jewish (ASJ)

AF:

0.00137

AC:

AN:

20424

East Asian (EAS)

AF:

0.00199

AC:

AN:

27604

South Asian (SAS)

AF:

0.00176

AC:

103

AN:

58576

European-Finnish (FIN)

AF:

0.000754

AC:

AN:

42444

Middle Eastern (MID)

AF:

0.00317

AC:

AN:

5046

European-Non Finnish (NFE)

AF:

0.000967

AC:

976

AN:

1008976

Other (OTH)

AF:

0.00327

AC:

166

AN:

50708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

170

254

339

424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.00670

AC:

991

AN:

147922

Hom.:

Cov.:

AF XY:

0.00670

AC XY:

484

AN XY:

72278

show subpopulations

African (AFR)

AF:

0.0200

AC:

807

AN:

40308

American (AMR)

AF:

0.00326

AC:

AN:

15016

Ashkenazi Jewish (ASJ)

AF:

0.00292

AC:

AN:

3420

East Asian (EAS)

AF:

0.00206

AC:

AN:

4866

South Asian (SAS)

AF:

0.00322

AC:

AN:

4656

European-Finnish (FIN)

AF:

0.000710

AC:

AN:

9854

Middle Eastern (MID)

AF:

0.00360

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00120

AC:

AN:

66586

Other (OTH)

AF:

0.00581

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

100

151

201

251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000632

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 13, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 10, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Dec 23, 2014

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Apr 14, 2017

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. -

Coffin-Siris syndrome 1

Benign:1

Aug 22, 2019

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was classified as: Likely benign. The following ACMG criteria were applied in classifying this variant: BS2,BP3,BP6. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.7

Mutation Taster

=78/22

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