rs587779748

Positions:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_001374828.1(ARID1B):c.1203_1205delAGG(p.Gly402del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,339,750 control chromosomes in the GnomAD database, including 89 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 11 hom., cov: 29)

Exomes 𝑓: 0.012 ( 78 hom. )

Consequence

ARID1B
NM_001374828.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.06

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001374828.1

BP6

Variant 6-156778871-CGGA-C is Benign according to our data. Variant chr6-156778871-CGGA-C is described in ClinVar as [Likely_benign]. Clinvar id is 126340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156778871-CGGA-C is described in Lovd as [Likely_benign]. Variant chr6-156778871-CGGA-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0092 (1351/146914) while in subpopulation SAS AF= 0.0151 (70/4650). AF 95% confidence interval is 0.0122. There are 11 homozygotes in gnomad4. There are 654 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1351 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1 linkuse as main transcript	c.1203_1205delAGG	p.Gly402del	disruptive_inframe_deletion	1/20	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2 linkuse as main transcript	c.1203_1205delAGG	p.Gly402del	disruptive_inframe_deletion	1/20	2	NM_001374828.1	ENSP00000490491.2		Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes

AF:

0.00921

AC:

1352

AN:

146820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00180

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.0430

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0150

Gnomad FIN

AF:

0.00506

Gnomad MID

AF:

0.0142

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.00846

GnomAD3 exomes

AF:

0.0119

AC:

513

AN:

43244

Hom.:

AF XY:

0.0130

AC XY:

330

AN XY:

25448

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00946

Gnomad ASJ exome

AF:

0.0409

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0138

Gnomad FIN exome

AF:

0.00487

Gnomad NFE exome

AF:

0.0111

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.0116

AC:

13853

AN:

1192836

Hom.:

AF XY:

0.0119

AC XY:

6930

AN XY:

583416

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00860

Gnomad4 ASJ exome

AF:

0.0432

Gnomad4 EAS exome

AF:

0.0000375

Gnomad4 SAS exome

AF:

0.0136

Gnomad4 FIN exome

AF:

0.00610

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.0131

GnomAD4 genome

AF:

0.00920

AC:

1351

AN:

146914

Hom.:

Cov.:

AF XY:

0.00912

AC XY:

654

AN XY:

71748

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.0430

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0151

Gnomad4 FIN

AF:

0.00506

Gnomad4 NFE

AF:

0.0116

Gnomad4 OTH

AF:

0.00839

Alfa

AF:

0.00861

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 06, 2020	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	ARID1B: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	Nov 03, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	May 27, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2016

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over