6-156779262-GCGCCGCCGC-GCGCCGCCGCCGC

Variant names:

• chr6-156779262-G-GCGC
• rs572236007
• NM_001374828.1:c.1597_1599dupCCG

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BA1

The NM_001374828.1(ARID1B):​c.1597_1599dupCCG​(p.Pro533dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.075 in 1,145,648 control chromosomes in the GnomAD database, including 3,584 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S534S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.064 (426 hom., cov: 28)
  • Exomes 𝑓: 0.077 (3158 hom.)
• Consequence: ARID1B NM_001374828.1 conservative_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.906
• Publications: 6 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

ENSG00000296922 (HGNC:):

ACMG classification

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

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156779262-G-GCGC is Benign according to our data. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779262-G-GCGC is described in CliVar as Benign. Clinvar id is 126314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.1597_1599dupCCG	p.Pro533dup	conservative_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	c.1597_1599dupCCG	p.Pro533dup	conservative_inframe_insertion	Exon 1 of 20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes AF: 0.0644 AC: 9007 AN: 139838 Hom.: 426 Cov.: 28

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.0337

Gnomad AMR AF: 0.0561

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.000221

Gnomad SAS AF: 0.0247

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0317

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.0628

GnomAD2 exomes AF: 0.0390 AC: 2531 AN: 64972 AF XY: 0.0400

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.0145

Gnomad ASJ exome AF: 0.0264

Gnomad EAS exome AF: 0.000365

Gnomad FIN exome AF: 0.0902

Gnomad NFE exome AF: 0.0532

Gnomad OTH exome AF: 0.0572

GnomAD4 exome AF: 0.0765 AC: 76940 AN: 1005698 Hom.: 3158 Cov.: 33 AF XY: 0.0752 AC XY: 36108 AN XY: 480220

African (AFR) AF: 0.0165 AC: 334 AN: 20280

American (AMR) AF: 0.0175 AC: 222 AN: 12720

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 304 AN: 10058

East Asian (EAS) AF: 0.0000506 AC: 1 AN: 19772

South Asian (SAS) AF: 0.0250 AC: 624 AN: 24952

European-Finnish (FIN) AF: 0.0768 AC: 1012 AN: 13178

Middle Eastern (MID) AF: 0.0342 AC: 91 AN: 2662

European-Non Finnish (NFE) AF: 0.0833 AC: 72117 AN: 865848

Other (OTH) AF: 0.0617 AC: 2235 AN: 36228

GnomAD4 genome AF: 0.0644 AC: 9008 AN: 139950 Hom.: 426 Cov.: 28 AF XY: 0.0666 AC XY: 4538 AN XY: 68106

African (AFR) AF: 0.0195 AC: 756 AN: 38820

American (AMR) AF: 0.0560 AC: 813 AN: 14506

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 131 AN: 3318

East Asian (EAS) AF: 0.000222 AC: 1 AN: 4508

South Asian (SAS) AF: 0.0249 AC: 113 AN: 4532

European-Finnish (FIN) AF: 0.172 AC: 1388 AN: 8056

Middle Eastern (MID) AF: 0.0336 AC: 8 AN: 238

European-Non Finnish (NFE) AF: 0.0894 AC: 5649 AN: 63196

Other (OTH) AF: 0.0622 AC: 121 AN: 1946

Alfa AF: 0.0301 Hom.: 53

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jan 24, 2014

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Mar 21, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.91
Mutation Taster		=88/12	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs572236007; hg19: chr6-157100396; COSMIC: COSV51649563; COSMIC: COSV51649563;