NM_001374828.1:c.1247_1255delGAGCAGGAG

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP3BP6BS1BS2

The NM_001374828.1(ARID1B):c.1247_1255delGAGCAGGAG(p.Gly416_Gly418del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,322,332 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 0.00039 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

ARID1B
NM_001374828.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 1.36

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:

ENSG00000296922 (HGNC:):

ENSG00000296922 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001374828.1

BP6

Variant 6-156778915-CAGGAGCAGG-C is Benign according to our data. Variant chr6-156778915-CAGGAGCAGG-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210315.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000392 (55/140424) while in subpopulation AFR AF = 0.000866 (33/38098). AF 95% confidence interval is 0.000633. There are 0 homozygotes in GnomAd4. There are 29 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High AC in GnomAd4 at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1 link	c.1247_1255delGAGCAGGAG	p.Gly416_Gly418del	disruptive_inframe_deletion	Exon 1 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.1247_1255delGAGCAGGAG	p.Gly416_Gly418del	disruptive_inframe_deletion	Exon 1 of 20	2	NM_001374828.1	ENSP00000490491.2		Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes

AF:

0.000392

AC:

AN:

140340

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000490

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000536

AC:

AN:

18646

AF XY:

0.0000889

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000228

AC:

269

AN:

1181908

Hom.:

AF XY:

0.000240

AC XY:

138

AN XY:

575624

show subpopulations

African (AFR)

AF:

0.000683

AC:

AN:

23442

American (AMR)

AF:

0.000481

AC:

AN:

10396

Ashkenazi Jewish (ASJ)

AF:

0.0000598

AC:

AN:

16712

East Asian (EAS)

AF:

0.000165

AC:

AN:

24310

South Asian (SAS)

AF:

0.000325

AC:

AN:

43118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3854

European-Non Finnish (NFE)

AF:

0.000227

AC:

222

AN:

976120

Other (OTH)

AF:

0.000146

AC:

AN:

47796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000392

AC:

AN:

140424

Hom.:

Cov.:

AF XY:

0.000422

AC XY:

AN XY:

68642

show subpopulations

African (AFR)

AF:

0.000866

AC:

AN:

38098

American (AMR)

AF:

0.000489

AC:

AN:

14306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3320

East Asian (EAS)

AF:

0.00

AC:

AN:

4356

South Asian (SAS)

AF:

0.00

AC:

AN:

4350

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9180

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

63830

Other (OTH)

AF:

0.00

AC:

AN:

1936

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

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 14, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 01, 2020

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Uncertain:1

Jan 12, 2015

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ARID1B-related disorder

Benign:1

May 19, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Inborn genetic diseases

Benign:1

Feb 08, 2018

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=188/12

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_001374828.1:c.1247_1255delGAGCAGGAG

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