6-156778268-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAG

Variant names:

• chr6-156778268-CCAGCAGCAG-C
• rs587779743
• NM_001374828.1:c.603_611delGCAGCAGCA

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.603_611delGCAGCAGCA​(p.Gln202_Gln204del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000292 in 1,536,818 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. Q201Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 3.90
• 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-CCAGCAGCAG-C is Benign according to our data. Variant chr6-156778268-CCAGCAGCAG-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 975342.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 = 0.00041 (62/151370) while in subpopulation AFR AF = 0.000896 (37/41288). AF 95% confidence interval is 0.000668. There are 0 homozygotes in GnomAd4. There are 44 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 62 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.603_611delGCAGCAGCA	p.Gln202_Gln204del	disruptive_inframe_deletion	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.603_611delGCAGCAGCA	p.Gln202_Gln204del	disruptive_inframe_deletion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.603_611delGCAGCAGCA	p.Gln202_Gln204del	disruptive_inframe_deletion	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.603_611delGCAGCAGCA	p.Gln202_Gln204del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.603_611delGCAGCAGCA	p.Gln202_Gln204del	disruptive_inframe_deletion	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.603_611delGCAGCAGCA	p.Gln202_Gln204del	disruptive_inframe_deletion	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.000403 AC: 61 AN: 151256 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000874

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000251

Gnomad OTH AF: 0.000962

GnomAD2 exomes AF: 0.000255 AC: 33 AN: 129416 AF XY: 0.000187

Gnomad AFR exome AF: 0.000464

Gnomad AMR exome AF: 0.000175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000425

Gnomad FIN exome AF: 0.000410

Gnomad NFE exome AF: 0.000271

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000279 AC: 386 AN: 1385448 Hom.: 0 AF XY: 0.000266 AC XY: 182 AN XY: 683558

African (AFR) AF: 0.00115 AC: 36 AN: 31376

American (AMR) AF: 0.000253 AC: 9 AN: 35514

Ashkenazi Jewish (ASJ) AF: 0.0000798 AC: 2 AN: 25064

East Asian (EAS) AF: 0.000169 AC: 6 AN: 35518

South Asian (SAS) AF: 0.000165 AC: 13 AN: 78742

European-Finnish (FIN) AF: 0.000193 AC: 8 AN: 41554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5578

European-Non Finnish (NFE) AF: 0.000272 AC: 292 AN: 1074394

Other (OTH) AF: 0.000347 AC: 20 AN: 57708

GnomAD4 genome AF: 0.000410 AC: 62 AN: 151370 Hom.: 0 Cov.: 30 AF XY: 0.000595 AC XY: 44 AN XY: 73994

African (AFR) AF: 0.000896 AC: 37 AN: 41288

American (AMR) AF: 0.000197 AC: 3 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5104

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10520

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000251 AC: 17 AN: 67668

Other (OTH) AF: 0.000952 AC: 2 AN: 2100

Alfa AF: 0.0000446 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 28, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Intellectual disability Benign:2

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

Jul 27, 2020

Cambridge Genomics Laboratory, East Genomic Laboratory Hub, NHS Genomic Medicine Service

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Inborn genetic diseases Benign:1

Dec 02, 2021

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 28, 2022

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).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9
Mutation Taster		=138/62	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;