NM_006015.6:c.3999_4001dupGCA

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_006015.6(ARID1A):c.3999_4001dupGCA(p.Gln1334dup) variant causes a disruptive inframe insertion, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,613,326 control chromosomes in the GnomAD database, including 25 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 21 hom. )

Consequence

ARID1A
NM_006015.6 disruptive_inframe_insertion, splice_region

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.65

Publications

23 publications found

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 Gene-Disease associations (from GenCC):

Coffin-Siris syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
intellectual disability, autosomal dominant 14
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae)

ARID1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_006015.6

BP6

Variant 1-26773690-C-CGCA is Benign according to our data. Variant chr1-26773690-C-CGCA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235338.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 = 0.00255 (387/152046) while in subpopulation SAS AF = 0.0181 (87/4816). AF 95% confidence interval is 0.015. There are 4 homozygotes in GnomAd4. There are 208 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 387 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6 link	c.3999_4001dupGCA	p.Gln1334dup	disruptive_inframe_insertion, splice_region_variant	Exon 16 of 20	ENST00000324856.13	NP_006006.3	O14497-1
ARID1A	NM_139135.4 link	c.3999_4001dupGCA	p.Gln1334dup	disruptive_inframe_insertion, splice_region_variant	Exon 16 of 20		NP_624361.1	O14497-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13 link	c.3999_4001dupGCA	p.Gln1334dup	disruptive_inframe_insertion, splice_region_variant	Exon 16 of 20	1	NM_006015.6	ENSP00000320485.7		O14497-1

Frequencies

GnomAD3 genomes

AF:

0.00249

AC:

378

AN:

151930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00305

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00443

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00172

Gnomad OTH

AF:

0.00288

GnomAD2 exomes

AF:

0.00400

AC:

975

AN:

243834

AF XY:

0.00494

show subpopulations

Gnomad AFR exome

AF:

0.00314

Gnomad AMR exome

AF:

0.00148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00366

Gnomad FIN exome

AF:

0.000384

Gnomad NFE exome

AF:

0.00187

Gnomad OTH exome

AF:

0.00267

GnomAD4 exome

AF:

0.00277

AC:

4046

AN:

1461280

Hom.:

Cov.:

AF XY:

0.00325

AC XY:

2363

AN XY:

726918

show subpopulations

African (AFR)

AF:

0.00263

AC:

AN:

33452

American (AMR)

AF:

0.00139

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00229

AC:

AN:

39680

South Asian (SAS)

AF:

0.0181

AC:

1561

AN:

86186

European-Finnish (FIN)

AF:

0.000356

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00178

AC:

1979

AN:

1111648

Other (OTH)

AF:

0.00386

AC:

233

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

288

576

863

1151

1439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<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:

0.00255

AC:

387

AN:

152046

Hom.:

Cov.:

AF XY:

0.00280

AC XY:

208

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00325

AC:

135

AN:

41496

American (AMR)

AF:

0.00124

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00444

AC:

AN:

5180

South Asian (SAS)

AF:

0.0181

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00172

AC:

117

AN:

67928

Other (OTH)

AF:

0.00285

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.00230

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jun 20, 2019

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

- -

Nov 23, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ARID1A: BS1, BS2 -

not specified

Benign:2

Aug 05, 2022

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Intellectual disability, autosomal dominant 14

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Mutation Taster

=71/29

polymorphism

(source)

Splicing

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