6-156778292-ACAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant names:

• chr6-156778292-A-ACAGCAGCAG
• rs587779744
• NM_001374828.1:c.627_635dupGCAGCAGCA

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3 BP6_Very_Strong BS2

The NM_001374828.1(ARID1B):​c.627_635dupGCAGCAGCA​(p.Gln210_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 0.000158 in 145,398 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00011 (0 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:5
• 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 -13 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778292-A-ACAGCAGCAG is Benign according to our data. Variant chr6-156778292-A-ACAGCAGCAG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 588939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 23 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.627_635dupGCAGCAGCA	p.Gln210_Gln212dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.627_635dupGCAGCAGCA	p.Gln210_Gln212dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.627_635dupGCAGCAGCA	p.Gln210_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.627_635dupGCAGCAGCA	p.Gln210_Gln212dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.627_635dupGCAGCAGCA	p.Gln210_Gln212dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.627_635dupGCAGCAGCA	p.Gln210_Gln212dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.000165 AC: 24 AN: 145298 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000303

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000267

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000202

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.0000957

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000893

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000222 AC: 28 AN: 126374 AF XY: 0.000221

Gnomad AFR exome AF: 0.000167

Gnomad AMR exome AF: 0.000488

Gnomad ASJ exome AF: 0.000130

Gnomad EAS exome AF: 0.000531

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000532

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000111 AC: 152 AN: 1372952 Hom.: 0 Cov.: 37 AF XY: 0.000120 AC XY: 81 AN XY: 677770

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

African (AFR) AF: 0.000178 AC: 5 AN: 28048

American (AMR) AF: 0.000399 AC: 14 AN: 35068

Ashkenazi Jewish (ASJ) AF: 0.0000403 AC: 1 AN: 24812

East Asian (EAS) AF: 0.000316 AC: 11 AN: 34776

South Asian (SAS) AF: 0.0000637 AC: 5 AN: 78520

European-Finnish (FIN) AF: 0.0000235 AC: 1 AN: 42484

Middle Eastern (MID) AF: 0.000362 AC: 2 AN: 5526

European-Non Finnish (NFE) AF: 0.0000947 AC: 101 AN: 1066896

Other (OTH) AF: 0.000211 AC: 12 AN: 56822

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000158 AC: 23 AN: 145398 Hom.: 0 Cov.: 31 AF XY: 0.000169 AC XY: 12 AN XY: 71144

African (AFR) AF: 0.000274 AC: 10 AN: 36450

American (AMR) AF: 0.000267 AC: 4 AN: 14986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.000202 AC: 1 AN: 4942

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4770

European-Finnish (FIN) AF: 0.0000957 AC: 1 AN: 10448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000893 AC: 6 AN: 67172

Other (OTH) AF: 0.00 AC: 0 AN: 2020

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ARID1B-related disorder Benign:1

Aug 16, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

Apr 06, 2017

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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.

Intellectual disability Benign:1

Jan 01, 2019

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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;