6-156778268-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAGCAGCAGCAG

Position:

• chr6-156778268-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BA1

The NM_001374828.1(ARID1B):​c.606_611dupGCAGCA​(p.Gln203_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 0.0035 in 1,536,714 control chromosomes in the GnomAD database, including 93 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. QQ204Q?) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.016 (63 hom., cov: 30)
  • Exomes 𝑓: 0.0021 (30 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 2.64

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]

ENSG00000271551 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778268-C-CCAGCAG is Benign according to our data. Variant chr6-156778268-C-CCAGCAG is described in ClinVar as [Likely_benign]. Clinvar id is 210284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.606_611dupGCAGCA	p.Gln203_Gln204dup	disruptive_inframe_insertion	1/20	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.606_611dupGCAGCA	p.Gln203_Gln204dup	disruptive_inframe_insertion	1/20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2468 AN: 151248 Hom.: 63 Cov.: 30

Gnomad AFR AF: 0.0555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00604

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000872

Gnomad OTH AF: 0.0130

GnomAD3 exomes AF: 0.00389 AC: 503 AN: 129416 Hom.: 5 AF XY: 0.00317 AC XY: 220 AN XY: 69488

Gnomad AFR exome AF: 0.0535

Gnomad AMR exome AF: 0.00380

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000532

Gnomad SAS exome AF: 0.000563

Gnomad FIN exome AF: 0.000103

Gnomad NFE exome AF: 0.000856

Gnomad OTH exome AF: 0.00290

GnomAD4 exome AF: 0.00210 AC: 2911 AN: 1385352 Hom.: 30 Cov.: 36 AF XY: 0.00187 AC XY: 1275 AN XY: 683512

Gnomad4 AFR exome AF: 0.0554

Gnomad4 AMR exome AF: 0.00417

Gnomad4 ASJ exome AF: 0.0000798

Gnomad4 EAS exome AF: 0.000310

Gnomad4 SAS exome AF: 0.000483

Gnomad4 FIN exome AF: 0.0000481

Gnomad4 NFE exome AF: 0.000662

Gnomad4 OTH exome AF: 0.00407

GnomAD4 genome AF: 0.0163 AC: 2466 AN: 151362 Hom.: 63 Cov.: 30 AF XY: 0.0159 AC XY: 1173 AN XY: 73992

Gnomad4 AFR AF: 0.0554

Gnomad4 AMR AF: 0.00603

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000872

Gnomad4 OTH AF: 0.0129

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Sep 30, 2015	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Coffin-Siris syndrome 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Sep 27, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 14, 2021	This variant is associated with the following publications: (PMID: 22405089) -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2018

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs587779743; hg19: chr6-157099402;