chr6-156778847-G-GGGCGGC

Position:

• chr6-156778847-G-GGGCGGC

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.1188_1193dupCGGCGG​(p.Gly397_Gly398dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0004 in 1,403,494 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00060 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• 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-GGGCGGC is Benign according to our data. Variant chr6-156778847-G-GGGCGGC is described in ClinVar as [Likely_benign]. Clinvar id is 210312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000602 (89/147924) while in subpopulation AMR AF= 0.00107 (16/15016). AF 95% confidence interval is 0.000668. There are 0 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 89 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.1188_1193dupCGGCGG	p.Gly397_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.1188_1193dupCGGCGG	p.Gly397_Gly398dup	disruptive_inframe_insertion	1/20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes AF: 0.000602 AC: 89 AN: 147820 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000373

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00107

Gnomad ASJ AF: 0.00585

Gnomad EAS AF: 0.000205

Gnomad SAS AF: 0.000429

Gnomad FIN AF: 0.000102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000481

Gnomad OTH AF: 0.000979

GnomAD3 exomes AF: 0.000234 AC: 13 AN: 55508 Hom.: 0 AF XY: 0.000244 AC XY: 8 AN XY: 32826

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000171

Gnomad ASJ exome AF: 0.00122

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000840

Gnomad FIN exome AF: 0.000241

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000377 AC: 473 AN: 1255570 Hom.: 0 Cov.: 37 AF XY: 0.000410 AC XY: 253 AN XY: 617172

Gnomad4 AFR exome AF: 0.000283

Gnomad4 AMR exome AF: 0.000410

Gnomad4 ASJ exome AF: 0.00568

Gnomad4 EAS exome AF: 0.000181

Gnomad4 SAS exome AF: 0.000597

Gnomad4 FIN exome AF: 0.0000707

Gnomad4 NFE exome AF: 0.000250

Gnomad4 OTH exome AF: 0.000808

GnomAD4 genome AF: 0.000602 AC: 89 AN: 147924 Hom.: 0 Cov.: 29 AF XY: 0.000553 AC XY: 40 AN XY: 72280

Gnomad4 AFR AF: 0.000372

Gnomad4 AMR AF: 0.00107

Gnomad4 ASJ AF: 0.00585

Gnomad4 EAS AF: 0.000206

Gnomad4 SAS AF: 0.000430

Gnomad4 FIN AF: 0.000102

Gnomad4 NFE AF: 0.000481

Gnomad4 OTH AF: 0.000969

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:5

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 14, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 11, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2021	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 17, 2015

- -

ARID1B-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 15, 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). -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 04, 2020

This alteration is classified as benign based on a combination of the following: 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: rs587779747; hg19: chr6-157099981;