1-26696649-TGGCGGCGGCGGCGGAGCC-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2

The NM_006015.6(ARID1A):c.250_267delGGCGGCGGCGGAGCCGGC(p.Gly84_Gly89del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.0000852 in 1,303,508 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 DEL_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 0.000061 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

ARID1A
NM_006015.6 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.35

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:

LOC124900417 (HGNC:):

LOC124900417 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_006015.6.

BP6

Variant 1-26696649-TGGCGGCGGCGGCGGAGCC-T is Benign according to our data. Variant chr1-26696649-TGGCGGCGGCGGCGGAGCC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1254549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000882 (102/1156852) while in subpopulation SAS AF = 0.00127 (49/38538). AF 95% confidence interval is 0.000988. There are 0 homozygotes in GnomAdExome4. There are 60 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

BS2

High AC in GnomAd4 at 9 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_267delGGCGGCGGCGGAGCCGGC	p.Gly84_Gly89del	conservative_inframe_deletion	Exon 1 of 20	NP_006006.3
	ARID1A	NM_139135.4		c.250_267delGGCGGCGGCGGAGCCGGC	p.Gly84_Gly89del	conservative_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.250_267delGGCGGCGGCGGAGCCGGC	p.Gly84_Gly89del	conservative_inframe_deletion	Exon 1 of 20	ENSP00000320485.7
ARID1A	ENST00000850904.1		c.250_267delGGCGGCGGCGGAGCCGGC	p.Gly84_Gly89del	conservative_inframe_deletion	Exon 1 of 20	ENSP00000520984.1
ARID1A	ENST00000457599.7	TSL:5	c.250_267delGGCGGCGGCGGAGCCGGC	p.Gly84_Gly89del	conservative_inframe_deletion	Exon 1 of 20	ENSP00000387636.2

Frequencies

GnomAD3 genomes

AF:

0.0000614

AC:

AN:

146546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000676

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000752

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00183

AC:

AN:

5474

AF XY:

0.00214

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000882

AC:

102

AN:

1156852

Hom.:

AF XY:

0.000107

AC XY:

AN XY:

561120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23278

American (AMR)

AF:

0.00

AC:

AN:

9018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15180

East Asian (EAS)

AF:

0.00

AC:

AN:

26944

South Asian (SAS)

AF:

0.00127

AC:

AN:

38538

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3116

European-Non Finnish (NFE)

AF:

0.0000497

AC:

AN:

964916

Other (OTH)

AF:

0.000108

AC:

AN:

46322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

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:

0.0000614

AC:

AN:

146656

Hom.:

Cov.:

AF XY:

0.0000559

AC XY:

AN XY:

71600

show subpopulations

African (AFR)

AF:

0.0000253

AC:

AN:

39584

American (AMR)

AF:

0.00

AC:

AN:

14900

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3424

East Asian (EAS)

AF:

0.00

AC:

AN:

4748

South Asian (SAS)

AF:

0.000675

AC:

AN:

4446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9898

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000752

AC:

AN:

66450

Other (OTH)

AF:

0.00

AC:

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

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:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

ARID1A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.3

Mutation Taster

=92/108

disease causing (long InDel)

(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