Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001374828.1(ARID1B):c.3828G>A(p.Glu1276Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,614,212 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 15 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 19 hom. )

Consequence

ARID1B
NM_001374828.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 3.09

Publications

4 publications found

Variant links:

COSMIC-nc: COSV104368481

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: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 6-157184344-G-A is Benign according to our data. Variant chr6-157184344-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 126326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.09 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.009 (1371/152318) while in subpopulation AFR AF = 0.0308 (1280/41564). AF 95% confidence interval is 0.0294. There are 15 homozygotes in GnomAd4. There are 642 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1371 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374828.1. 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.3828G>A	p.Glu1276Glu	synonymous	Exon 13 of 20	NP_001361757.1
ARID1B	NM_001438482.1		c.3957G>A	p.Glu1319Glu	synonymous	Exon 14 of 21	NP_001425411.1
ARID1B	NM_001438483.1		c.3870G>A	p.Glu1290Glu	synonymous	Exon 14 of 21	NP_001425412.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.3828G>A	p.Glu1276Glu	synonymous	Exon 13 of 20	ENSP00000490491.2
ARID1B	ENST00000346085.10	TSL:1	c.3708G>A	p.Glu1236Glu	synonymous	Exon 14 of 21	ENSP00000344546.5
ARID1B	ENST00000350026.11	TSL:1	c.3669G>A	p.Glu1223Glu	synonymous	Exon 12 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes

AF:

0.00901

AC:

1372

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0309

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00272

AC:

684

AN:

251456

AF XY:

0.00210

show subpopulations

Gnomad AFR exome

AF:

0.0365

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000325

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00108

AC:

1586

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000884

AC XY:

643

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.0345

AC:

1154

AN:

33480

American (AMR)

AF:

0.00163

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000210

AC:

234

AN:

1112012

Other (OTH)

AF:

0.00195

AC:

118

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

188

281

375

469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.00900

AC:

1371

AN:

152318

Hom.:

Cov.:

AF XY:

0.00862

AC XY:

642

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0308

AC:

1280

AN:

41564

American (AMR)

AF:

0.00353

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000367

AC:

AN:

68030

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

132

197

263

329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00456

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

ARID1B-related disorder (1)

Coffin-Siris syndrome 1 (1)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

rs61745451

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