rs375160616

Variant summary

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

The NM_001374828.1(ARID1B):c.985G>A(p.Gly329Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00563 in 1,488,164 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G329A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0047 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0057 ( 31 hom. )

Consequence

ARID1B
NM_001374828.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.438

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049165785).

BP6

Variant 6-156778665-G-A is Benign according to our data. Variant chr6-156778665-G-A is described in ClinVar as [Benign]. Clinvar id is 210310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156778665-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00472 (708/149844) while in subpopulation AMR AF= 0.00758 (115/15166). AF 95% confidence interval is 0.00646. There are 1 homozygotes in gnomad4. There are 290 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd at 711 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1 linkuse as main transcript	c.985G>A	p.Gly329Ser	missense_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.985G>A	p.Gly329Ser	missense_variant	1/20	2	NM_001374828.1	A2	Q8NFD5-3

Frequencies

GnomAD3 genomes

AF:

0.00475

AC:

711

AN:

149736

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00119

Gnomad AMI

AF:

0.0541

Gnomad AMR

AF:

0.00759

Gnomad ASJ

AF:

0.00905

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00188

Gnomad FIN

AF:

0.00138

Gnomad MID

AF:

0.0227

Gnomad NFE

AF:

0.00628

Gnomad OTH

AF:

0.00778

GnomAD3 exomes

AF:

0.00477

AC:

471

AN:

98838

Hom.:

AF XY:

0.00460

AC XY:

254

AN XY:

55228

show subpopulations

Gnomad AFR exome

AF:

0.000458

Gnomad AMR exome

AF:

0.00412

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00257

Gnomad FIN exome

AF:

0.00150

Gnomad NFE exome

AF:

0.00652

Gnomad OTH exome

AF:

0.00716

GnomAD4 exome

AF:

0.00573

AC:

7668

AN:

1338320

Hom.:

Cov.:

AF XY:

0.00557

AC XY:

3677

AN XY:

660118

show subpopulations

Gnomad4 AFR exome

AF:

0.00189

Gnomad4 AMR exome

AF:

0.00473

Gnomad4 ASJ exome

AF:

0.0101

Gnomad4 EAS exome

AF:

0.0000329

Gnomad4 SAS exome

AF:

0.00248

Gnomad4 FIN exome

AF:

0.00145

Gnomad4 NFE exome

AF:

0.00625

Gnomad4 OTH exome

AF:

0.00576

GnomAD4 genome

AF:

0.00472

AC:

708

AN:

149844

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

290

AN XY:

73176

show subpopulations

Gnomad4 AFR

AF:

0.00119

Gnomad4 AMR

AF:

0.00758

Gnomad4 ASJ

AF:

0.00905

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00188

Gnomad4 FIN

AF:

0.00138

Gnomad4 NFE

AF:

0.00625

Gnomad4 OTH

AF:

0.00771

Alfa

AF:

0.00617

Hom.:

Bravo

AF:

0.00539

ExAC

AF:

0.00315

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 06, 2018	This variant is associated with the following publications: (PMID: 26845707) -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 06, 2017	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	ARID1B: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
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	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 16, 2015

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 12, 2016

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

0.068

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.51

T;T;T;T

MetaRNN

Benign

0.0049

T;T;T;T

MetaSVM

Benign

-0.90

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Pathogenic

0.87

REVEL

Benign

0.060

Polyphen

0.0010

.;B;.;B

Vest4

0.12

MVP

0.093

MPC

0.29

ClinPred

0.076

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.19

gMVP

0.13

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