6-156778292-ACAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAG

Variant names:

• chr6-156778292-A-ACAG
• rs587779744
• NM_001374828.1:c.633_635dupGCA

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The NM_001374828.1(ARID1B):​c.633_635dupGCA​(p.Gln212dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,518,244 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q212Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0039 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (9 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.46
• Publications: 12 publications found

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

ENSG00000271551 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778292-A-ACAG is Benign according to our data. Variant chr6-156778292-A-ACAG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00393 (572/145396) while in subpopulation SAS AF = 0.0132 (63/4770). AF 95% confidence interval is 0.0106. There are 5 homozygotes in GnomAd4. There are 280 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 572 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	NM_001374828.1	MANE Select	c.633_635dupGCA	p.Gln212dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.633_635dupGCA	p.Gln212dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.633_635dupGCA	p.Gln212dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425412.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.633_635dupGCA	p.Gln212dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.633_635dupGCA	p.Gln212dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.633_635dupGCA	p.Gln212dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.00390 AC: 567 AN: 145296 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000668

Gnomad ASJ AF: 0.00234

Gnomad EAS AF: 0.00343

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00327

Gnomad NFE AF: 0.000953

Gnomad OTH AF: 0.00400

GnomAD2 exomes AF: 0.00345 AC: 436 AN: 126374 AF XY: 0.00420

Gnomad AFR exome AF: 0.00954

Gnomad AMR exome AF: 0.000888

Gnomad ASJ exome AF: 0.00326

Gnomad EAS exome AF: 0.000955

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000838

Gnomad OTH exome AF: 0.00319

GnomAD4 exome AF: 0.00171 AC: 2346 AN: 1372848 Hom.: 9 Cov.: 37 AF XY: 0.00206 AC XY: 1393 AN XY: 677718

African (AFR) AF: 0.0108 AC: 303 AN: 28028

American (AMR) AF: 0.000827 AC: 29 AN: 35068

Ashkenazi Jewish (ASJ) AF: 0.00258 AC: 64 AN: 24812

East Asian (EAS) AF: 0.00423 AC: 147 AN: 34776

South Asian (SAS) AF: 0.0116 AC: 907 AN: 78508

European-Finnish (FIN) AF: 0.000141 AC: 6 AN: 42484

Middle Eastern (MID) AF: 0.000543 AC: 3 AN: 5526

European-Non Finnish (NFE) AF: 0.000741 AC: 791 AN: 1066834

Other (OTH) AF: 0.00169 AC: 96 AN: 56812

GnomAD4 genome AF: 0.00393 AC: 572 AN: 145396 Hom.: 5 Cov.: 31 AF XY: 0.00394 AC XY: 280 AN XY: 71144

African (AFR) AF: 0.0110 AC: 401 AN: 36448

American (AMR) AF: 0.000667 AC: 10 AN: 14986

Ashkenazi Jewish (ASJ) AF: 0.00234 AC: 8 AN: 3414

East Asian (EAS) AF: 0.00344 AC: 17 AN: 4942

South Asian (SAS) AF: 0.0132 AC: 63 AN: 4770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10448

Middle Eastern (MID) AF: 0.00350 AC: 1 AN: 286

European-Non Finnish (NFE) AF: 0.000953 AC: 64 AN: 67172

Other (OTH) AF: 0.00396 AC: 8 AN: 2020

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Mar 11, 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)

Sep 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

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Apr 01, 2019

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Inborn genetic diseases Benign:1

Sep 22, 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.

ARID1B-related disorder Benign:1

Mar 19, 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).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=77/23	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs587779744; hg19: chr6-157099426; COSMIC: COSV51675034;