1-26696885-TCGCCGCCGC-TCGC

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM4BS2

The NM_006015.6(ARID1A):c.489_494delCGCCGC(p.Ala164_Ala165del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000512 in 1,348,618 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A163A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

ARID1A
NM_006015.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02

Publications

1 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: Likely_benign. The variant received -2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_006015.6.

BS2

High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006015.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1A	NM_006015.6	MANE Select	c.489_494delCGCCGC	p.Ala164_Ala165del	disruptive_inframe_deletion	Exon 1 of 20	NP_006006.3
	ARID1A	NM_139135.4		c.489_494delCGCCGC	p.Ala164_Ala165del	disruptive_inframe_deletion	Exon 1 of 20	NP_624361.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARID1A	ENST00000324856.13	TSL:1 MANE Select	c.489_494delCGCCGC	p.Ala164_Ala165del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000320485.7
ARID1A	ENST00000850904.1		c.489_494delCGCCGC	p.Ala164_Ala165del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000520984.1
ARID1A	ENST00000457599.7	TSL:5	c.489_494delCGCCGC	p.Ala164_Ala165del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000387636.2

Frequencies

GnomAD3 genomes

AF:

0.0000411

AC:

AN:

145868

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000764

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000671

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000223

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000420

AC:

AN:

23828

AF XY:

0.0000758

show subpopulations

Gnomad AFR exome

AF:

0.000954

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:

0.0000524

AC:

AN:

1202618

Hom.:

AF XY:

0.0000600

AC XY:

AN XY:

583276

show subpopulations

African (AFR)

AF:

0.000126

AC:

AN:

23872

American (AMR)

AF:

0.000105

AC:

AN:

9544

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15920

East Asian (EAS)

AF:

0.0000729

AC:

AN:

27428

South Asian (SAS)

AF:

0.0000211

AC:

AN:

47436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40012

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4700

European-Non Finnish (NFE)

AF:

0.0000548

AC:

AN:

985418

Other (OTH)

AF:

0.0000414

AC:

AN:

48288

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

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

AF:

0.0000411

AC:

AN:

146000

Hom.:

Cov.:

AF XY:

0.0000421

AC XY:

AN XY:

71308

show subpopulations

African (AFR)

AF:

0.0000762

AC:

AN:

39370

American (AMR)

AF:

0.0000671

AC:

AN:

14910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3414

East Asian (EAS)

AF:

0.000223

AC:

AN:

4478

South Asian (SAS)

AF:

0.00

AC:

AN:

4372

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66152

Other (OTH)

AF:

0.00

AC:

AN:

2036

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

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Oct 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant, c.489_494del, results in the deletion of 2 amino acid(s) of the ARID1A protein (p.Ala166_Ala167del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs759913677, gnomAD 0.06%). This variant has been observed in individual(s) with clinical features of Coffin-Siris syndrome (PMID: 35801292). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.0

Mutation Taster

=117/83

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over