1-26697417-GGCTGCGGCGGCGGCA-GGCTGCGGCGGCGGCAGCTGCGGCGGCGGCA

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_006015.6(ARID1A):c.1029_1043dupAGCTGCGGCGGCGGC(p.Ala344_Ala348dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,350,952 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

ARID1A
NM_006015.6 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.08

Publications

0 publications found

Variant links:

COSMIC-nc: COSV99081684

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 -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_006015.6

BP6

Variant 1-26697417-G-GGCTGCGGCGGCGGCA is Benign according to our data. Variant chr1-26697417-G-GGCTGCGGCGGCGGCA is described in ClinVar as Likely_benign. ClinVar VariationId is 2193229.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 26 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.1029_1043dupAGCTGCGGCGGCGGC	p.Ala344_Ala348dup	disruptive_inframe_insertion	Exon 1 of 20	NP_006006.3
	ARID1A	NM_139135.4		c.1029_1043dupAGCTGCGGCGGCGGC	p.Ala344_Ala348dup	disruptive_inframe_insertion	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.1029_1043dupAGCTGCGGCGGCGGC	p.Ala344_Ala348dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000320485.7
ARID1A	ENST00000850904.1		c.1029_1043dupAGCTGCGGCGGCGGC	p.Ala344_Ala348dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000520984.1
ARID1A	ENST00000457599.7	TSL:5	c.1029_1043dupAGCTGCGGCGGCGGC	p.Ala344_Ala348dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000387636.2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151700

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000217

AC:

AN:

1199136

Hom.:

Cov.:

AF XY:

0.0000274

AC XY:

AN XY:

583536

show subpopulations

African (AFR)

AF:

0.0000422

AC:

AN:

23700

American (AMR)

AF:

0.000111

AC:

AN:

9006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16246

East Asian (EAS)

AF:

0.0000362

AC:

AN:

27642

South Asian (SAS)

AF:

0.0000639

AC:

AN:

46924

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3312

European-Non Finnish (NFE)

AF:

0.0000181

AC:

AN:

995080

Other (OTH)

AF:

0.0000406

AC:

AN:

49276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.0000132

AC:

AN:

151816

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74192

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5096

South Asian (SAS)

AF:

0.000208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67834

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Mutation Taster

=78/22

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over