rs751352361

Positions:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_006015.6(ARID1A):c.1029_1043delAGCTGCGGCGGCGGC(p.Ala344_Ala348del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000626 in 1,350,944 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 4 hom. )

Consequence

ARID1A
NM_006015.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 2.51

Variant links:

Genes affected

ARID1A (HGNC:11110): (AT-rich interaction domain 1A) This gene encodes a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. It possesses at least two conserved domains that could be important for its function. First, it has a DNA-binding domain that can specifically bind an AT-rich DNA sequence known to be recognized by a SNF/SWI complex at the beta-globin locus. Second, the C-terminus of the protein can stimulate glucocorticoid receptor-dependent transcriptional activation. It is thought that the protein encoded by this gene confers specificity to the SNF/SWI complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ARID1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-26697417-GGCTGCGGCGGCGGCA-G is Benign according to our data. Variant chr1-26697417-GGCTGCGGCGGCGGCA-G is described in ClinVar as [Likely_benign]. Clinvar id is 434336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00083 (126/151816) while in subpopulation SAS AF= 0.00208 (10/4810). AF 95% confidence interval is 0.00113. There are 0 homozygotes in gnomad4. There are 60 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 126 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1A	NM_006015.6 linkuse as main transcript	c.1029_1043delAGCTGCGGCGGCGGC	p.Ala344_Ala348del	disruptive_inframe_deletion	1/20	ENST00000324856.13	NP_006006.3	O14497-1
ARID1A	NM_139135.4 linkuse as main transcript	c.1029_1043delAGCTGCGGCGGCGGC	p.Ala344_Ala348del	disruptive_inframe_deletion	1/20		NP_624361.1	O14497-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARID1A	ENST00000324856.13 linkuse as main transcript	c.1029_1043delAGCTGCGGCGGCGGC	p.Ala344_Ala348del	disruptive_inframe_deletion	1/20	1	NM_006015.6	ENSP00000320485.7	O14497-1
ARID1A	ENST00000457599.6 linkuse as main transcript	c.1029_1043delAGCTGCGGCGGCGGC	p.Ala344_Ala348del	disruptive_inframe_deletion	1/20	5		ENSP00000387636.2	O14497-2
ARID1A	ENST00000430799.7 linkuse as main transcript	c.-13+3815_-13+3829delAGCTGCGGCGGCGGC		intron_variant		5		ENSP00000390317.3	H0Y488
ARID1A	ENST00000637465.1 linkuse as main transcript	c.-13+1332_-13+1346delAGCTGCGGCGGCGGC		intron_variant		5		ENSP00000490650.1	A0A1B0GVT5

Frequencies

GnomAD3 genomes

AF:

0.000831

AC:

126

AN:

151700

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000895

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.000782

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000766

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00275

AC:

AN:

1092

Hom.:

AF XY:

0.00442

AC XY:

AN XY:

678

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 SAS exome

AF:

0.0273

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000600

AC:

720

AN:

1199128

Hom.:

AF XY:

0.000588

AC XY:

343

AN XY:

583532

show subpopulations

Gnomad4 AFR exome

AF:

0.000886

Gnomad4 AMR exome

AF:

0.000999

Gnomad4 ASJ exome

AF:

0.000554

Gnomad4 EAS exome

AF:

0.000904

Gnomad4 SAS exome

AF:

0.00181

Gnomad4 FIN exome

AF:

0.000250

Gnomad4 NFE exome

AF:

0.000522

Gnomad4 OTH exome

AF:

0.000893

GnomAD4 genome

AF:

0.000830

AC:

126

AN:

151816

Hom.:

Cov.:

AF XY:

0.000809

AC XY:

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.000892

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00116

Gnomad4 EAS

AF:

0.000785

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000767

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000162

Hom.:

Bravo

AF:

0.000884

Asia WGS

AF:

0.00174

AC:

AN:

3458

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 25, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	ARID1A: BS1 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 30, 2021

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2021

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. -

ARID1A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 29, 2023

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

Intellectual disability, autosomal dominant 14

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Leipzig Medical Center

Jan 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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