rs773423003

chr6-156778906-GAGGAGGAGCAGGAGC-Gchr6-156778906-GAGGAGGAGCAGGAGC-GAGGAGGAGCAGGAGCAGGAGGAGCAGGAGC

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.1242_1256del(p.Gly416_Gly420del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,367,030 control chromosomes in the GnomAD database, including 46 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 29)
  • Exomes 𝑓: 0.0014 (44 hom.)
• Consequence: ARID1B NM_001374828.1 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5 O:1
• Conservation: PhyloP100: 1.80

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778906-GAGGAGGAGCAGGAGC-G is Benign according to our data. Variant chr6-156778906-GAGGAGGAGCAGGAGC-G is described in ClinVar as [Likely_benign]. Clinvar id is 434355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.1242_1256del	p.Gly416_Gly420del	inframe_deletion	1/20	ENST00000636930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.1242_1256del	p.Gly416_Gly420del	inframe_deletion	1/20	2	NM_001374828.1	A2

Frequencies

GnomAD3 genomes AF: 0.00115 AC: 170 AN: 148222 Hom.: 2 Cov.: 29

Gnomad AFR AF: 0.000173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00414

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0178

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000195

Gnomad OTH AF: 0.000492

GnomAD3 exomes AF: 0.000149 AC: 4 AN: 26778 Hom.: 0 AF XY: 0.000124 AC XY: 2 AN XY: 16184

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00549

Gnomad SAS exome AF: 0.000190

Gnomad FIN exome AF: 0.000237

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00140 AC: 1704 AN: 1218704 Hom.: 44 AF XY: 0.00139 AC XY: 826 AN XY: 595740

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.00173

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0549

Gnomad4 SAS exome AF: 0.0000806

Gnomad4 FIN exome AF: 0.000180

Gnomad4 NFE exome AF: 0.000110

Gnomad4 OTH exome AF: 0.00105

GnomAD4 genome AF: 0.00115 AC: 170 AN: 148326 Hom.: 2 Cov.: 29 AF XY: 0.00121 AC XY: 88 AN XY: 72486

Gnomad4 AFR AF: 0.000197

Gnomad4 AMR AF: 0.00413

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0177

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000195

Gnomad4 OTH AF: 0.000486

Alfa AF: 0.000759 Hom.: 0

Asia WGS AF: 0.00988 AC: 35 AN: 3454

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 28, 2021	This variant is associated with the following publications: (PMID: 22405089) -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 21, 2016

- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2019

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

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 18, 2020

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). -

Coffin-Siris syndrome 1 Other:1

not provided, no classification provided

phenotyping only

GenomeConnect - Invitae Patient Insights Network

-

Variant interpreted as Uncertain significance and reported on 04-14-2021 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. -

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: rs773423003; hg19: chr6-157100040;