6-156778268-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAGCAGCAG

Position:

chr6-156778268-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAGCAGCAG

Variant summary

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

The NM_001374828.1(ARID1B):c.609_611dupGCA(p.Gln204dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 151,370 control chromosomes in the GnomAD database, including 26 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. QQ204Q?) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.012 ( 26 hom., cov: 30)

Exomes 𝑓: 0.0046 ( 17 hom. )

Failed GnomAD Quality Control

Consequence

ARID1B
NM_001374828.1 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.64

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:

ENSG00000271551 (HGNC:):

ENSG00000271551 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 6-156778268-C-CCAG is Benign according to our data. Variant chr6-156778268-C-CCAG is described in ClinVar as [Likely_benign]. Clinvar id is 126327.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 = 0.012 (1822/151370) while in subpopulation AFR AF= 0.0316 (1305/41288). AF 95% confidence interval is 0.0302. There are 26 homozygotes in gnomad4. There are 858 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1822 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1 linkuse as main transcript	c.609_611dupGCA	p.Gln204dup	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.609_611dupGCA	p.Gln204dup	disruptive_inframe_insertion	1/20	2	NM_001374828.1	ENSP00000490491.2		Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1816

AN:

151256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00420

Gnomad ASJ

AF:

0.00203

Gnomad EAS

AF:

0.0233

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.00228

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00395

Gnomad OTH

AF:

0.0135

GnomAD3 exomes

AF:

0.00640

AC:

828

AN:

129416

Hom.:

AF XY:

0.00534

AC XY:

371

AN XY:

69488

show subpopulations

Gnomad AFR exome

AF:

0.0300

Gnomad AMR exome

AF:

0.00624

Gnomad ASJ exome

AF:

0.00101

Gnomad EAS exome

AF:

0.0219

Gnomad SAS exome

AF:

0.00141

Gnomad FIN exome

AF:

0.00195

Gnomad NFE exome

AF:

0.00432

Gnomad OTH exome

AF:

0.00553

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00463

AC:

6418

AN:

1385256

Hom.:

Cov.:

AF XY:

0.00451

AC XY:

3081

AN XY:

683452

show subpopulations

Gnomad4 AFR exome

AF:

0.0320

Gnomad4 AMR exome

AF:

0.00572

Gnomad4 ASJ exome

AF:

0.00112

Gnomad4 EAS exome

AF:

0.0189

Gnomad4 SAS exome

AF:

0.00152

Gnomad4 FIN exome

AF:

0.00250

Gnomad4 NFE exome

AF:

0.00368

Gnomad4 OTH exome

AF:

0.00530

GnomAD4 genome

AF:

0.0120

AC:

1822

AN:

151370

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

858

AN XY:

73994

show subpopulations

Gnomad4 AFR

AF:

0.0316

Gnomad4 AMR

AF:

0.00426

Gnomad4 ASJ

AF:

0.00203

Gnomad4 EAS

AF:

0.0235

Gnomad4 SAS

AF:

0.00146

Gnomad4 FIN

AF:

0.00228

Gnomad4 NFE

AF:

0.00393

Gnomad4 OTH

AF:

0.0133

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 17, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Mar 17, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	ARID1B: BS1 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 09, 2017

- -

ARID1B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 18, 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). -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 16, 2018

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. -

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