NM_006015.6:c.57_62delGCCGCC

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP3BP6_Moderate

The NM_006015.6(ARID1A):c.57_62delGCCGCC(p.Pro20_Pro21del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,285,662 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ARID1A
NM_006015.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.57

Publications

2 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: Likely_benign. The variant received -3 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_006015.6

BP6

Variant 1-26696448-CCCGCCG-C is Benign according to our data. Variant chr1-26696448-CCCGCCG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1700510.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6 link	c.57_62delGCCGCC	p.Pro20_Pro21del	disruptive_inframe_deletion	Exon 1 of 20	ENST00000324856.13	NP_006006.3	O14497-1
ARID1A	NM_139135.4 link	c.57_62delGCCGCC	p.Pro20_Pro21del	disruptive_inframe_deletion	Exon 1 of 20		NP_624361.1	O14497-2
LOC124900417	XM_047439473.1 link	c.-49_-44delCGGCGG		upstream_gene_variant			XP_047295429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13 link	c.57_62delGCCGCC	p.Pro20_Pro21del	disruptive_inframe_deletion	Exon 1 of 20	1	NM_006015.6	ENSP00000320485.7		O14497-1

Frequencies

GnomAD3 genomes

AF:

0.0000272

AC:

AN:

147056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000748

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:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1138606

Hom.:

AF XY:

0.00000724

AC XY:

AN XY:

552420

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

23118

American (AMR)

AF:

0.00

AC:

AN:

11628

Ashkenazi Jewish (ASJ)

AF:

0.0000630

AC:

AN:

15868

East Asian (EAS)

AF:

0.0000387

AC:

AN:

25810

South Asian (SAS)

AF:

0.0000524

AC:

AN:

38184

European-Finnish (FIN)

AF:

0.0000420

AC:

AN:

23836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3086

European-Non Finnish (NFE)

AF:

0.0000116

AC:

AN:

951890

Other (OTH)

AF:

0.0000443

AC:

AN:

45186

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000238106), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.328

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:

0.0000272

AC:

AN:

147056

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

71886

show subpopulations

African (AFR)

AF:

0.0000748

AC:

AN:

40130

American (AMR)

AF:

0.00

AC:

AN:

14928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3410

East Asian (EAS)

AF:

0.00

AC:

AN:

4988

South Asian (SAS)

AF:

0.00

AC:

AN:

4698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66094

Other (OTH)

AF:

0.00

AC:

AN:

2022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 11, 2022

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.6

Mutation Taster

=120/80

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