rs112474841

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001374828.1(ARID1B):c.1194A>C(p.Gly398=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,340,260 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 29)

Exomes 𝑓: 0.0012 ( 11 hom. )

Consequence

ARID1B
NM_001374828.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.06

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-156778874-A-C is Benign according to our data. Variant chr6-156778874-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 434353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156778874-A-C is described in Lovd as [Benign]. Variant chr6-156778874-A-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.07 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.002 (270/135162) while in subpopulation AMR AF= 0.00202 (28/13840). AF 95% confidence interval is 0.00162. There are 1 homozygotes in gnomad4. There are 135 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd at 270 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1 linkuse as main transcript	c.1194A>C	p.Gly398=	synonymous_variant	1/20	ENST00000636930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2 linkuse as main transcript	c.1194A>C	p.Gly398=	synonymous_variant	1/20	2	NM_001374828.1	A2	Q8NFD5-3

Frequencies

GnomAD3 genomes

AF:

0.00200

AC:

270

AN:

135056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.0286

Gnomad EAS

AF:

0.00136

Gnomad SAS

AF:

0.000485

Gnomad FIN

AF:

0.000112

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.00105

Gnomad OTH

AF:

0.00429

GnomAD3 exomes

AF:

0.00150

AC:

AN:

51868

Hom.:

AF XY:

0.00147

AC XY:

AN XY:

30590

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.0141

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000630

Gnomad FIN exome

AF:

0.0000851

Gnomad NFE exome

AF:

0.000602

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00119

AC:

1440

AN:

1205098

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

721

AN XY:

591454

show subpopulations

Gnomad4 AFR exome

AF:

0.00210

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.0251

Gnomad4 EAS exome

AF:

0.000366

Gnomad4 SAS exome

AF:

0.000516

Gnomad4 FIN exome

AF:

0.0000491

Gnomad4 NFE exome

AF:

0.000703

Gnomad4 OTH exome

AF:

0.00276

GnomAD4 genome

AF:

0.00200

AC:

270

AN:

135162

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

135

AN XY:

66042

show subpopulations

Gnomad4 AFR

AF:

0.00199

Gnomad4 AMR

AF:

0.00202

Gnomad4 ASJ

AF:

0.0286

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.000485

Gnomad4 FIN

AF:

0.000112

Gnomad4 NFE

AF:

0.00105

Gnomad4 OTH

AF:

0.00424

Alfa

AF:

0.00278

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	ARID1B: BP4, BP7, BS1 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2018	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 12, 2015	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 06, 2016

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. -

Coffin-Siris syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

ARID1B-related condition

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 02, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

Cadd

Benign

Dann

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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