rs199948752

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M512I) has been classified as Uncertain significance.

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

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

Coffin-Siris syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina, ClinGen
Coffin-Siris syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ARID1B links:

ENSG00000296922 (HGNC:):

ENSG00000296922 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 126312.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 = 0.000576 (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 the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High AC in GnomAd4 at 82 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1 link	c.1534A>G	p.Met512Val	missense_variant	Exon 1 of 20	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2 link	c.1534A>G	p.Met512Val	missense_variant	Exon 1 of 20	2	NM_001374828.1	ENSP00000490491.2

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

GnomAD2 exomes

AF:

0.000664

AC:

AN:

124960

AF XY:

0.000746

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 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

African (AFR)

AF:

0.0000434

AC:

AN:

23020

American (AMR)

AF:

0.000236

AC:

AN:

21144

Ashkenazi Jewish (ASJ)

AF:

0.00141

AC:

AN:

15558

East Asian (EAS)

AF:

0.00

AC:

AN:

24878

South Asian (SAS)

AF:

0.00

AC:

AN:

41306

European-Finnish (FIN)

AF:

0.000697

AC:

AN:

24394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4322

European-Non Finnish (NFE)

AF:

0.000796

AC:

746

AN:

936816

Other (OTH)

AF:

0.000680

AC:

AN:

42638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

108

163

217

271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000576

AC:

AN:

142412

Hom.:

Cov.:

AF XY:

0.000692

AC XY:

AN XY:

69362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39082

American (AMR)

AF:

0.00130

AC:

AN:

14588

Ashkenazi Jewish (ASJ)

AF:

0.00177

AC:

AN:

3382

East Asian (EAS)

AF:

0.00

AC:

AN:

4450

South Asian (SAS)

AF:

0.00

AC:

AN:

4424

European-Finnish (FIN)

AF:

0.000809

AC:

AN:

8658

Middle Eastern (MID)

AF:

0.00

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.000773

AC:

AN:

64722

Other (OTH)

AF:

0.00

AC:

AN:

1986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000695

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

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ARID1B: BS1, BS2 -

Nov 19, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 12, 2019

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ARID1B-related disorder

Benign:1

Jul 15, 2022

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Dec 21, 2018

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

4.1

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

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.25

gMVP

0.60

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over