1-26696649-TGGCGGCGGCGGCGGAGCC-TGGCGGCGGCGGCGGAGCCGGCGGCGGCGGCGGAGCC

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM4BP6BS2

The NM_006015.6(ARID1A):c.250_267dupGGCGGCGGCGGAGCCGGC(p.Gly84_Gly89dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,303,392 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000048 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ARID1A
NM_006015.6 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.67

Publications

1 publications found

Variant links:

COSMIC-nc: COSV109426806

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:

LOC124900417 (HGNC:):

LOC124900417 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_006015.6.

BP6

Variant 1-26696649-T-TGGCGGCGGCGGCGGAGCC is Benign according to our data. Variant chr1-26696649-T-TGGCGGCGGCGGCGGAGCC is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 434312.

BS2

High AC in GnomAd4 at 7 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.250_267dupGGCGGCGGCGGAGCCGGC	p.Gly84_Gly89dup	conservative_inframe_insertion	Exon 1 of 20	NP_006006.3
	ARID1A	NM_139135.4		c.250_267dupGGCGGCGGCGGAGCCGGC	p.Gly84_Gly89dup	conservative_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.250_267dupGGCGGCGGCGGAGCCGGC	p.Gly84_Gly89dup	conservative_inframe_insertion	Exon 1 of 20	ENSP00000320485.7
ARID1A	ENST00000850904.1		c.250_267dupGGCGGCGGCGGAGCCGGC	p.Gly84_Gly89dup	conservative_inframe_insertion	Exon 1 of 20	ENSP00000520984.1
ARID1A	ENST00000457599.7	TSL:5	c.250_267dupGGCGGCGGCGGAGCCGGC	p.Gly84_Gly89dup	conservative_inframe_insertion	Exon 1 of 20	ENSP00000387636.2

Frequencies

GnomAD3 genomes

AF:

0.0000478

AC:

AN:

146546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000451

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000173

AC:

200

AN:

1156846

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

103

AN XY:

561118

show subpopulations

African (AFR)

AF:

0.000172

AC:

AN:

23278

American (AMR)

AF:

0.000111

AC:

AN:

9016

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15180

East Asian (EAS)

AF:

0.0000742

AC:

AN:

26944

South Asian (SAS)

AF:

0.0000259

AC:

AN:

38542

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3116

European-Non Finnish (NFE)

AF:

0.000196

AC:

189

AN:

964908

Other (OTH)

AF:

0.0000648

AC:

AN:

46322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.0000478

AC:

AN:

146546

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71476

show subpopulations

African (AFR)

AF:

0.000101

AC:

AN:

39480

American (AMR)

AF:

0.00

AC:

AN:

14880

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3424

East Asian (EAS)

AF:

0.00

AC:

AN:

4760

South Asian (SAS)

AF:

0.00

AC:

AN:

4440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9898

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000451

AC:

AN:

66458

Other (OTH)

AF:

0.00

AC:

AN:

2022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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.:

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Coffin-Siris syndrome (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.7

Mutation Taster

=77/23

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over