6-156778909-GAGGAGC-GAGGAGCAGGAGC

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The NM_001374828.1(ARID1B):c.1241_1246dup(p.Ala414_Gly415dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000391 in 1,352,964 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00052 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00037 (0 hom.)
• Consequence: ARID1B NM_001374828.1 inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.50

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 6-156778909-G-GAGGAGC is Benign according to our data. Variant chr6-156778909-G-GAGGAGC is described in ClinVar as [Likely_benign]. Clinvar id is 588355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000523 (77/147142) while in subpopulation EAS AF= 0.00217 (10/4618). AF 95% confidence interval is 0.00117. There are 0 homozygotes in gnomad4. There are 38 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd at 77 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.1241_1246dup	p.Ala414_Gly415dup	inframe_insertion	1/20	ENST00000636930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.1241_1246dup	p.Ala414_Gly415dup	inframe_insertion	1/20	2	NM_001374828.1	A2

Frequencies

GnomAD3 genomes AF: 0.000524 AC: 77 AN: 147042 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00216

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00719

Gnomad NFE AF: 0.000436

Gnomad OTH AF: 0.00149

GnomAD3 exomes AF: 0.0000842 AC: 2 AN: 23744 Hom.: 0 AF XY: 0.000139 AC XY: 2 AN XY: 14358

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00543

Gnomad SAS exome AF: 0.000223

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000375 AC: 452 AN: 1205822 Hom.: 0 Cov.: 35 AF XY: 0.000338 AC XY: 199 AN XY: 588806

Gnomad4 AFR exome AF: 0.000421

Gnomad4 AMR exome AF: 0.000691

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00250

Gnomad4 SAS exome AF: 0.000147

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000334

Gnomad4 OTH exome AF: 0.000532

GnomAD4 genome AF: 0.000523 AC: 77 AN: 147142 Hom.: 0 Cov.: 30 AF XY: 0.000529 AC XY: 38 AN XY: 71842

Gnomad4 AFR AF: 0.000746

Gnomad4 AMR AF: 0.000202

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00217

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000436

Gnomad4 OTH AF: 0.00147

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 02, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	ARID1B: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 22, 2022	- -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2018

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. -

ARID1B-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 24, 2022

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 v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs747438636; hg19: chr6-157100043;