6-157207091-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBS2_Supporting

The NM_001374828.1(ARID1B):c.6319G>A(p.Glu2107Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,890 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ARID1B
NM_001374828.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.16

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.16764995).

BP6

Variant 6-157207091-G-A is Benign according to our data. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-157207091-G-A is described in CliVar as Likely_benign. Clinvar id is 3061959.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1 link	c.6319G>A	p.Glu2107Lys	missense_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.6319G>A	p.Glu2107Lys	missense_variant	Exon 20 of 20	2	NM_001374828.1	ENSP00000490491.2		Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251340

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

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:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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.:

Alfa

AF:

0.00000431

Hom.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Coffin-Siris syndrome 1

Benign:1

Mar 14, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.033

.;T;.;.;T;.;T;.;.;T

Eigen

Benign

-0.071

Eigen_PC

Benign

0.066

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.0069

MetaRNN

Benign

0.17

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;N;.;.;.;.;.;.;.;.

PhyloP100

3.2

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.24

.;N;.;.;N;.;.;.;.;.

REVEL

Benign

0.089

Sift

Benign

0.36

.;T;.;.;T;.;.;.;.;.

Sift4G

Benign

0.94

.;T;.;.;T;.;.;.;.;.

Polyphen

0.82, 0.79

.;P;.;P;.;.;.;.;.;.

Vest4

0.33

MutPred

0.34

.;Gain of methylation at E1971 (P = 0.004);.;.;.;.;.;.;.;.;

MVP

0.57

MPC

1.5

ClinPred

0.64

GERP RS

4.4

PromoterAI

-0.010

Neutral

(source)

Varity_R

0.15

gMVP

0.48

Mutation Taster

=70/30

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over