rs762183842

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The ENST00000636930.2(ARID1B):c.5240G>A(p.Arg1747Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,507,434 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000081 ( 0 hom. )

Consequence

ARID1B
ENST00000636930.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 7.70

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP6

Variant 6-157201465-G-A is Benign according to our data. Variant chr6-157201465-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 434389.

BS2

High AC in GnomAdExome4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636930.2. 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.5240G>A	p.Arg1747Gln	missense	Exon 18 of 20	NP_001361757.1
ARID1B	NM_001438482.1		c.5369G>A	p.Arg1790Gln	missense	Exon 19 of 21	NP_001425411.1
ARID1B	NM_001438483.1		c.5282G>A	p.Arg1761Gln	missense	Exon 19 of 21	NP_001425412.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.5240G>A	p.Arg1747Gln	missense	Exon 18 of 20	ENSP00000490491.2
ARID1B	ENST00000346085.10	TSL:1	c.5120G>A	p.Arg1707Gln	missense	Exon 19 of 21	ENSP00000344546.5
ARID1B	ENST00000350026.11	TSL:1	c.5081G>A	p.Arg1694Gln	missense	Exon 17 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000173

AC:

AN:

173204

AF XY:

0.0000109

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000645

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000118

Gnomad OTH exome

AF:

0.000253

GnomAD4 exome

AF:

0.00000812

AC:

AN:

1355142

Hom.:

Cov.:

AF XY:

0.00000755

AC XY:

AN XY:

661884

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30066

American (AMR)

AF:

0.00

AC:

AN:

28344

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19980

East Asian (EAS)

AF:

0.0000522

AC:

AN:

38322

South Asian (SAS)

AF:

0.00

AC:

AN:

69532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5284

European-Non Finnish (NFE)

AF:

0.00000755

AC:

AN:

1058930

Other (OTH)

AF:

0.0000179

AC:

AN:

55750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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

AF:

0.0000197

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41552

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000167

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Coffin-Siris syndrome 1 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

7.7

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.42

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.85

MutPred

0.39

Gain of ubiquitination at K1608 (P = 0.0317)

MVP

0.62

MPC

1.6

ClinPred

0.89

GERP RS

4.8

Varity_R

0.53

gMVP

0.49

Mutation Taster

=53/47

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over