6-156778847-GGGCGGCGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGCGGC

Position:

• chr6-156778847-GGGCGGCGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGCGGC

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.1191_1193dupCGG​(p.Gly398dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00216 in 1,403,452 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G398G) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0067 (6 hom., cov: 29)
  • Exomes 𝑓: 0.0016 (14 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• 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-G-GGGC is Benign according to our data. Variant chr6-156778847-G-GGGC is described in ClinVar as [Likely_benign]. Clinvar id is 210313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0067 (991/147922) while in subpopulation AFR AF= 0.02 (807/40308). AF 95% confidence interval is 0.0189. There are 6 homozygotes in gnomad4. There are 484 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 991 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.1191_1193dupCGG	p.Gly398dup	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.1191_1193dupCGG	p.Gly398dup	disruptive_inframe_insertion	1/20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes AF: 0.00671 AC: 992 AN: 147818 Hom.: 6 Cov.: 29

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00292

Gnomad EAS AF: 0.00205

Gnomad SAS AF: 0.00322

Gnomad FIN AF: 0.000710

Gnomad MID AF: 0.00333

Gnomad NFE AF: 0.00120

Gnomad OTH AF: 0.00588

GnomAD3 exomes AF: 0.00104 AC: 58 AN: 55508 Hom.: 0 AF XY: 0.00107 AC XY: 35 AN XY: 32826

Gnomad AFR exome AF: 0.0179

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.00122

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00118

Gnomad FIN exome AF: 0.000563

Gnomad NFE exome AF: 0.000634

Gnomad OTH exome AF: 0.00155

GnomAD4 exome AF: 0.00163 AC: 2043 AN: 1255530 Hom.: 14 Cov.: 37 AF XY: 0.00161 AC XY: 993 AN XY: 617140

Gnomad4 AFR exome AF: 0.0243

Gnomad4 AMR exome AF: 0.00387

Gnomad4 ASJ exome AF: 0.00137

Gnomad4 EAS exome AF: 0.00199

Gnomad4 SAS exome AF: 0.00176

Gnomad4 FIN exome AF: 0.000754

Gnomad4 NFE exome AF: 0.000967

Gnomad4 OTH exome AF: 0.00327

GnomAD4 genome AF: 0.00670 AC: 991 AN: 147922 Hom.: 6 Cov.: 29 AF XY: 0.00670 AC XY: 484 AN XY: 72278

Gnomad4 AFR AF: 0.0200

Gnomad4 AMR AF: 0.00326

Gnomad4 ASJ AF: 0.00292

Gnomad4 EAS AF: 0.00206

Gnomad4 SAS AF: 0.00322

Gnomad4 FIN AF: 0.000710

Gnomad4 NFE AF: 0.00120

Gnomad4 OTH AF: 0.00581

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Mar 10, 2017	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 23, 2014

- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 14, 2017

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. -

Coffin-Siris syndrome 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Aug 22, 2019

This variant was classified as: Likely benign. The following ACMG criteria were applied in classifying this variant: BS2,BP3,BP6. -

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;