dbSNP rs878853084: ARID1B:p.Ala423Glu (chr6-156778948-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001374828.1(ARID1B):c.1268C>A(p.Ala423Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000689 in 145,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A423V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARID1B
NM_001374828.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.14

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21194175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1 link	c.1268C>A	p.Ala423Glu	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.1268C>A	p.Ala423Glu	missense_variant	Exon 1 of 20	2	NM_001374828.1	ENSP00000490491.2		Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes

AF:

0.00000689

AC:

AN:

145190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1137650

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

548414

African (AFR)

AF:

0.00

AC:

AN:

23152

American (AMR)

AF:

0.00

AC:

AN:

8820

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14936

East Asian (EAS)

AF:

0.00

AC:

AN:

26948

South Asian (SAS)

AF:

0.00

AC:

AN:

28188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3260

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

957896

Other (OTH)

AF:

0.00

AC:

AN:

45958

GnomAD4 genome

AF:

0.00000689

AC:

AN:

145190

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70974

show subpopulations

African (AFR)

AF:

0.0000254

AC:

AN:

39316

American (AMR)

AF:

0.00

AC:

AN:

14828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

4720

South Asian (SAS)

AF:

0.00

AC:

AN:

4552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65670

Other (OTH)

AF:

0.00

AC:

AN:

1966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.012

.;T;.;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.35

T;T;T;T

M_CAP

Pathogenic

0.71

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;N;N

PhyloP100

2.1

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

0.59

.;N;.;.

REVEL

Benign

0.071

Sift

Benign

0.11

.;T;.;.

Sift4G

Benign

0.12

.;T;.;.

Polyphen

0.88, 0.93

.;P;.;P

Vest4

0.33

MutPred

0.35

.;Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);

MVP

0.10

MPC

0.34

ClinPred

0.21

GERP RS

1.4

PromoterAI

-0.024

Neutral

(source)

Varity_R

0.13

gMVP

0.23

Mutation Taster

=87/13

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over