6-156778847-GGGCGGCGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGCGGCGGC

Position:

chr6-156778847-GGGCGGCGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGCGGCGGC

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

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

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 4.68

Variant links:

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]

ARID1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	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 linkuse as main transcript	c.1188_1193dupCGGCGG	p.Gly397_Gly398dup	disruptive_inframe_insertion	1/20	2	NM_001374828.1	ENSP00000490491.2		Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes

AF:

0.000602

AC:

AN:

147820

Hom.:

Cov.:

show subpopulations

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:

AN:

55508

Hom.:

AF XY:

0.000244

AC XY:

AN XY:

32826

show subpopulations

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.:

Cov.:

AF XY:

0.000410

AC XY:

253

AN XY:

617172

show subpopulations

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:

AN:

147924

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

AN XY:

72280

show subpopulations

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

LINK: link

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

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over