rs199948752

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001374828.1(ARID1B):c.1534A>G(p.Met512Val) variant causes a missense change. The variant allele was found at a frequency of 0.000707 in 1,276,488 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00058 ( 1 hom., cov: 30)

Exomes 𝑓: 0.00072 ( 0 hom. )

Consequence

ARID1B
NM_001374828.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.10

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030590057).

BP6

Variant 6-156779214-A-G is Benign according to our data. Variant chr6-156779214-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 126312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156779214-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000576 (82/142412) while in subpopulation AMR AF= 0.0013 (19/14588). AF 95% confidence interval is 0.000852. There are 1 homozygotes in gnomad4. There are 48 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 82 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1 linkuse as main transcript	c.1534A>G	p.Met512Val	missense_variant	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.1534A>G	p.Met512Val	missense_variant	1/20	2	NM_001374828.1	ENSP00000490491	A2	Q8NFD5-3

Frequencies

GnomAD3 genomes

AF:

0.000576

AC:

AN:

142296

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00130

Gnomad ASJ

AF:

0.00177

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000809

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000772

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000664

AC:

AN:

124960

Hom.:

AF XY:

0.000746

AC XY:

AN XY:

73716

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000139

Gnomad ASJ exome

AF:

0.00116

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000596

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.000392

GnomAD4 exome

AF:

0.000723

AC:

820

AN:

1134076

Hom.:

Cov.:

AF XY:

0.000708

AC XY:

393

AN XY:

555462

show subpopulations

Gnomad4 AFR exome

AF:

0.0000434

Gnomad4 AMR exome

AF:

0.000236

Gnomad4 ASJ exome

AF:

0.00141

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000697

Gnomad4 NFE exome

AF:

0.000796

Gnomad4 OTH exome

AF:

0.000680

GnomAD4 genome

AF:

0.000576

AC:

AN:

142412

Hom.:

Cov.:

AF XY:

0.000692

AC XY:

AN XY:

69362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00130

Gnomad4 ASJ

AF:

0.00177

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000809

Gnomad4 NFE

AF:

0.000773

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000533

Hom.:

Bravo

AF:

0.000465

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000422

AC:

ExAC

AF:

0.000626

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 19, 2020	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	ARID1B: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 28, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 12, 2019

- -

ARID1B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2022

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

Dec 21, 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. -

Coffin-Siris syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Benign

0.54

DEOGEN2

Benign

0.017

.;T;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.83

T;T;T;T

M_CAP

Pathogenic

0.74

MetaRNN

Benign

0.031

T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.0

.;L;L;L

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.79

.;N;.;.

REVEL

Benign

0.11

Sift

Benign

0.054

.;T;.;.

Sift4G

Benign

0.11

.;T;.;.

Polyphen

0.78, 0.86

.;P;.;P

Vest4

0.30

MVP

0.19

MPC

0.32

ClinPred

0.049

GERP RS

2.2

Varity_R

0.25

gMVP

0.60

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