6-156778847-GGGCGGCGGCGGCGGCGGC-GGGCGGCGGC

Position:

• chr6-156778847-GGGCGGCGGCGGCGGCGGC-GGGCGGCGGC

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.1185_1193delCGGCGGCGG​(p.Gly396_Gly398del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00199 in 1,403,448 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (3 hom., cov: 29)
  • Exomes 𝑓: 0.0019 (7 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 4.68

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 6-156778847-GGGCGGCGGC-G is Benign according to our data. Variant chr6-156778847-GGGCGGCGGC-G is described in ClinVar as [Likely_benign]. Clinvar id is 434371.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 = 0.00267 (395/147916) while in subpopulation EAS AF= 0.00637 (31/4864). AF 95% confidence interval is 0.00461. There are 3 homozygotes in gnomad4. There are 213 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 395 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.1185_1193delCGGCGGCGG	p.Gly396_Gly398del	disruptive_inframe_deletion	1/20	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.1185_1193delCGGCGGCGG	p.Gly396_Gly398del	disruptive_inframe_deletion	1/20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes AF: 0.00266 AC: 393 AN: 147812 Hom.: 3 Cov.: 29

Gnomad AFR AF: 0.00343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00147

Gnomad ASJ AF: 0.000878

Gnomad EAS AF: 0.00656

Gnomad SAS AF: 0.00172

Gnomad FIN AF: 0.00670

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00176

Gnomad OTH AF: 0.00343

GnomAD3 exomes AF: 0.00247 AC: 137 AN: 55508 Hom.: 3 AF XY: 0.00219 AC XY: 72 AN XY: 32826

Gnomad AFR exome AF: 0.00198

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.000245

Gnomad EAS exome AF: 0.00797

Gnomad SAS exome AF: 0.000925

Gnomad FIN exome AF: 0.00723

Gnomad NFE exome AF: 0.00116

Gnomad OTH exome AF: 0.00155

GnomAD4 exome AF: 0.00191 AC: 2395 AN: 1255532 Hom.: 7 AF XY: 0.00188 AC XY: 1160 AN XY: 617146

Gnomad4 AFR exome AF: 0.00336

Gnomad4 AMR exome AF: 0.00135

Gnomad4 ASJ exome AF: 0.00122

Gnomad4 EAS exome AF: 0.00732

Gnomad4 SAS exome AF: 0.00133

Gnomad4 FIN exome AF: 0.00888

Gnomad4 NFE exome AF: 0.00146

Gnomad4 OTH exome AF: 0.00256

GnomAD4 genome AF: 0.00267 AC: 395 AN: 147916 Hom.: 3 Cov.: 29 AF XY: 0.00295 AC XY: 213 AN XY: 72274

Gnomad4 AFR AF: 0.00347

Gnomad4 AMR AF: 0.00147

Gnomad4 ASJ AF: 0.000878

Gnomad4 EAS AF: 0.00637

Gnomad4 SAS AF: 0.00172

Gnomad4 FIN AF: 0.00670

Gnomad4 NFE AF: 0.00176

Gnomad4 OTH AF: 0.00388

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	ARID1B: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 16, 2015

- -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2024

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Coffin-Siris syndrome 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 30, 2022

- -

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: rs587779747; hg19: chr6-157099981;