rs140177120

chr6-157203986-A-Gchr6-157203986-A-T

Variant summary

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

The NM_001374828.1(ARID1B):c.5384A>G(p.Asn1795Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000942 in 1,614,060 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. N1795I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00096 ( 2 hom. )

Consequence

ARID1B
NM_001374828.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.63

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=0.027790278).

BP6

Variant 6-157203986-A-G is Benign according to our data. Variant chr6-157203986-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 210297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000749 (114/152304) while in subpopulation NFE AF= 0.00106 (72/68024). AF 95% confidence interval is 0.000861. There are 0 homozygotes in gnomad4. There are 58 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd at 114 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1 linkuse as main transcript	c.5384A>G	p.Asn1795Ser	missense_variant	19/20	ENST00000636930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2 linkuse as main transcript	c.5384A>G	p.Asn1795Ser	missense_variant	19/20	2	NM_001374828.1	A2	Q8NFD5-3

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

114

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000799

AC:

201

AN:

251482

Hom.:

AF XY:

0.000750

AC XY:

102

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.000878

Gnomad NFE exome

AF:

0.000985

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000963

AC:

1407

AN:

1461756

Hom.:

Cov.:

AF XY:

0.000909

AC XY:

661

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.000554

Gnomad4 SAS exome

AF:

0.000568

Gnomad4 FIN exome

AF:

0.000524

Gnomad4 NFE exome

AF:

0.00104

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.000749

AC:

114

AN:

152304

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000958

Hom.:

Bravo

AF:

0.000816

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000749

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000771

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2019	This variant is associated with the following publications: (PMID: 31332282, 22405089, 27824329, 25363768) -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	ARID1B: BP4, BS1 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 12, 2024	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 14, 2020

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2019

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. -

ARID1B-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 17, 2022

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). -

Coffin-Siris syndrome 1

Benign:1

Likely 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

0.058

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.70

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.0067

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.87

D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.0037

MetaRNN

Benign

0.028

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

0.88

D;D;D;D

PrimateAI

Uncertain

0.49

REVEL

Benign

0.13

Polyphen

0.016, 0.027

.;B;.;B;.;.;.;.;.

Vest4

0.11

MVP

0.36

MPC

0.44

ClinPred

0.027

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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