rs1455234951

Positions:

chr6-156778909-G-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2

The NM_001374828.1(ARID1B):c.1229G>C(p.Gly410Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000739 in 1,352,872 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

ARID1B
NM_001374828.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:2

Conservation

PhyloP100: 1.06

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10892236).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000177 (26/147044) while in subpopulation AFR AF= 0.000424 (17/40128). AF 95% confidence interval is 0.00027. There are 0 homozygotes in gnomad4. There are 15 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1 linkuse as main transcript	c.1229G>C	p.Gly410Ala	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.1229G>C	p.Gly410Ala	missense_variant	1/20	2	NM_001374828.1	ENSP00000490491.2		Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

147044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000424

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000135

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000105

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000614

AC:

AN:

1205828

Hom.:

Cov.:

AF XY:

0.0000577

AC XY:

AN XY:

588806

show subpopulations

Gnomad4 AFR exome

AF:

0.000464

Gnomad4 AMR exome

AF:

0.0000864

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000210

Gnomad4 FIN exome

AF:

0.0000267

Gnomad4 NFE exome

AF:

0.0000586

Gnomad4 OTH exome

AF:

0.0000205

GnomAD4 genome

AF:

0.000177

AC:

AN:

147044

Hom.:

Cov.:

AF XY:

0.000209

AC XY:

AN XY:

71742

show subpopulations

Gnomad4 AFR

AF:

0.000424

Gnomad4 AMR

AF:

0.000135

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000105

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000245

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Coffin-Siris syndrome 1

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 31, 2018	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Sep 22, 2017	The G327A variant in the ARID1B gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The G327A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G327A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret G327A as a variant of uncertain significance. -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 05, 2024	- -

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2016

The p.G327A variant (also known as c.980G>C), located in coding exon 1 of the ARID1B gene, results from a G to C substitution at nucleotide position 980. The glycine at codon 327 is replaced by alanine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

ARID1B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 10, 2023

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.014

.;T;.;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.29

T;T;T;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

.;N;N;N

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.13

.;N;.;.

REVEL

Benign

0.024

Sift

Pathogenic

0.0

.;D;.;.

Sift4G

Benign

1.0

.;T;.;.

Polyphen

0.025, 0.043

.;B;.;B

Vest4

0.21

MutPred

0.29

.;Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);

MVP

0.12

MPC

0.31

ClinPred

0.30

GERP RS

1.9

Varity_R

0.088

gMVP

0.28

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