NM_001374828.1:c.6291C>T

Variant names:

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.6291C>T(p.Ile2097Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00937 in 1,614,160 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0095 ( 99 hom. )

Consequence

ARID1B
NM_001374828.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.33

Publications

5 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: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 6-157207063-C-T is Benign according to our data. Variant chr6-157207063-C-T is described in ClinVar as Benign. ClinVar VariationId is 126336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.33 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00814 (1240/152270) while in subpopulation NFE AF = 0.0117 (794/68018). AF 95% confidence interval is 0.011. There are 10 homozygotes in GnomAd4. There are 574 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1240 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1 link	c.6291C>T	p.Ile2097Ile	synonymous_variant	Exon 20 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.6291C>T	p.Ile2097Ile	synonymous_variant	Exon 20 of 20	2	NM_001374828.1	ENSP00000490491.2		Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes

AF:

0.00814

AC:

1239

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00936

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00933

Gnomad FIN

AF:

0.00981

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.00814

GnomAD2 exomes

AF:

0.00991

AC:

2489

AN:

251250

AF XY:

0.0106

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00682

Gnomad ASJ exome

AF:

0.00586

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.00950

AC:

13881

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00980

AC XY:

7127

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

33480

American (AMR)

AF:

0.00693

AC:

310

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00620

AC:

162

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0132

AC:

1142

AN:

86258

European-Finnish (FIN)

AF:

0.0114

AC:

607

AN:

53416

Middle Eastern (MID)

AF:

0.0199

AC:

115

AN:

5768

European-Non Finnish (NFE)

AF:

0.00983

AC:

10934

AN:

1112012

Other (OTH)

AF:

0.00932

AC:

563

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1055

2110

3164

4219

5274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.00814

AC:

1240

AN:

152270

Hom.:

Cov.:

AF XY:

0.00771

AC XY:

574

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00202

AC:

AN:

41568

American (AMR)

AF:

0.00934

AC:

143

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00955

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00981

AC:

104

AN:

10600

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0117

AC:

794

AN:

68018

Other (OTH)

AF:

0.00806

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

128

193

257

321

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:

0.00882

Hom.:

Bravo

AF:

0.00783

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.0157

EpiControl

AF:

0.0140

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ARID1B: BP4, BS1, BS2 -

Sep 15, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Oct 23, 2015

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

May 15, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Coffin-Siris syndrome 1

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

1.3

PromoterAI

-0.0072

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over