Genetic Variant ARID1B:p.Gly95Arg (chr6-156777963-G-C) – 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_001438482.1(ARID1B):c.283G>C(p.Gly95Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,378,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. G95S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

ARID1B
NM_001438482.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.253

Publications

0 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:

ENSG00000271551 (HGNC:):

ENSG00000271551 links:

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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=0.149335).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438482.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARID1B	NM_001374828.1	MANE Select	c.283G>C	p.Gly95Arg	missense	Exon 1 of 20	NP_001361757.1
ARID1B	NM_001438482.1		c.283G>C	p.Gly95Arg	missense	Exon 1 of 21	NP_001425411.1
ARID1B	NM_001438483.1		c.283G>C	p.Gly95Arg	missense	Exon 1 of 21	NP_001425412.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.283G>C	p.Gly95Arg	missense	Exon 1 of 20	ENSP00000490491.2
ARID1B	ENST00000346085.10	TSL:1	c.283G>C	p.Gly95Arg	missense	Exon 2 of 21	ENSP00000344546.5
ARID1B	ENST00000350026.11	TSL:1	c.283G>C	p.Gly95Arg	missense	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.26e-7

AC:

AN:

1378280

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

680018

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31226

American (AMR)

AF:

0.00

AC:

AN:

35110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24978

East Asian (EAS)

AF:

0.00

AC:

AN:

35512

South Asian (SAS)

AF:

0.00

AC:

AN:

78702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33954

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4242

European-Non Finnish (NFE)

AF:

9.28e-7

AC:

AN:

1077026

Other (OTH)

AF:

0.00

AC:

AN:

57530

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

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.012

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.0091

LIST_S2

Benign

0.39

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.0

PhyloP100

0.25

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.050

REVEL

Benign

0.021

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.049

Vest4

0.065

MutPred

0.25

Gain of helix (P = 0.005)

MVP

0.093

MPC

0.35

ClinPred

0.14

GERP RS

-2.0

PromoterAI

-0.030

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.14

gMVP

0.49

Mutation Taster

=95/5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over