NM_001374828.1:c.609_611dupGCA

Variant names:

• chr6-156778268-C-CCAG
• rs587779743
• NM_001374828.1:c.609_611dupGCA

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.609_611dupGCA​(p.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 0.012 in 151,370 control chromosomes in the GnomAD database, including 26 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 0.012 (26 hom., cov: 30)
  • Exomes 𝑓: 0.0046 (17 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.64
• Publications: 5 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 6-156778268-C-CCAG is Benign according to our data. Variant chr6-156778268-C-CCAG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 126327.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 = 0.012 (1822/151370) while in subpopulation AFR AF = 0.0316 (1305/41288). AF 95% confidence interval is 0.0302. There are 26 homozygotes in GnomAd4. There are 858 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1822 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.609_611dupGCA	p.Gln204dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.609_611dupGCA	p.Gln204dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.609_611dupGCA	p.Gln204dup	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.609_611dupGCA	p.Gln204dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.609_611dupGCA	p.Gln204dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.609_611dupGCA	p.Gln204dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1816 AN: 151256 Hom.: 25 Cov.: 30

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00420

Gnomad ASJ AF: 0.00203

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.00228

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00395

Gnomad OTH AF: 0.0135

GnomAD2 exomes AF: 0.00640 AC: 828 AN: 129416 AF XY: 0.00534

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.00624

Gnomad ASJ exome AF: 0.00101

Gnomad EAS exome AF: 0.0219

Gnomad FIN exome AF: 0.00195

Gnomad NFE exome AF: 0.00432

Gnomad OTH exome AF: 0.00553

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00463 AC: 6418 AN: 1385256 Hom.: 17 Cov.: 36 AF XY: 0.00451 AC XY: 3081 AN XY: 683452

African (AFR) AF: 0.0320 AC: 1002 AN: 31346

American (AMR) AF: 0.00572 AC: 203 AN: 35516

Ashkenazi Jewish (ASJ) AF: 0.00112 AC: 28 AN: 25064

East Asian (EAS) AF: 0.0189 AC: 672 AN: 35510

South Asian (SAS) AF: 0.00152 AC: 120 AN: 78738

European-Finnish (FIN) AF: 0.00250 AC: 104 AN: 41552

Middle Eastern (MID) AF: 0.00466 AC: 26 AN: 5578

European-Non Finnish (NFE) AF: 0.00368 AC: 3957 AN: 1074260

Other (OTH) AF: 0.00530 AC: 306 AN: 57692

GnomAD4 genome AF: 0.0120 AC: 1822 AN: 151370 Hom.: 26 Cov.: 30 AF XY: 0.0116 AC XY: 858 AN XY: 73994

African (AFR) AF: 0.0316 AC: 1305 AN: 41288

American (AMR) AF: 0.00426 AC: 65 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00203 AC: 7 AN: 3450

East Asian (EAS) AF: 0.0235 AC: 120 AN: 5104

South Asian (SAS) AF: 0.00146 AC: 7 AN: 4790

European-Finnish (FIN) AF: 0.00228 AC: 24 AN: 10520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00393 AC: 266 AN: 67668

Other (OTH) AF: 0.0133 AC: 28 AN: 2100

Alfa AF: 0.00174 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Sep 17, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ARID1B: BS1

Mar 17, 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

Aug 09, 2017

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Inborn genetic diseases Benign:1

Jul 16, 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.

ARID1B-related disorder Benign:1

Feb 18, 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		2.6
Mutation Taster		=80/20	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs587779743; hg19: chr6-157099402; COSMIC: COSV51651299; COSMIC: COSV51651299;