1-26696516-AGGCGGCGGCGGC-AGGCGGC

Variant names:

• chr1-26696516-AGGCGGC-A
• rs587779737
• NM_006015.6:c.123_128delGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_006015.6(ARID1A):​c.123_128delGGCGGC​(p.Ala42_Ala43del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000735 in 1,224,588 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A41A) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: ARID1A NM_006015.6 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.84
• Publications: 5 publications found

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)

LOC124900417 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_006015.6.
• BP6: Variant 1-26696516-AGGCGGC-A is Benign according to our data. Variant chr1-26696516-AGGCGGC-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2914471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 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.123_128delGGCGGC	p.Ala42_Ala43del	disruptive_inframe_deletion	Exon 1 of 20	NP_006006.3
	ARID1A	NM_139135.4		c.123_128delGGCGGC	p.Ala42_Ala43del	disruptive_inframe_deletion	Exon 1 of 20	NP_624361.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1A	ENST00000324856.13	TSL:1 MANE Select	c.123_128delGGCGGC	p.Ala42_Ala43del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000320485.7
	ARID1A	ENST00000850904.1		c.123_128delGGCGGC	p.Ala42_Ala43del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000520984.1
	ARID1A	ENST00000457599.7	TSL:5	c.123_128delGGCGGC	p.Ala42_Ala43del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000387636.2

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149104 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000246

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: 0.0000991

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000651 AC: 7 AN: 1075484 Hom.: 0 AF XY: 0.00000980 AC XY: 5 AN XY: 510436

African (AFR) AF: 0.0000450 AC: 1 AN: 22238

American (AMR) AF: 0.00 AC: 0 AN: 7890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13582

East Asian (EAS) AF: 0.00 AC: 0 AN: 25310

South Asian (SAS) AF: 0.00 AC: 0 AN: 21164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2858

European-Non Finnish (NFE) AF: 0.00000653 AC: 6 AN: 918526

Other (OTH) AF: 0.00 AC: 0 AN: 42746

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 149104 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 72786

African (AFR) AF: 0.0000246 AC: 1 AN: 40586

American (AMR) AF: 0.00 AC: 0 AN: 15062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 4918

South Asian (SAS) AF: 0.00 AC: 0 AN: 4678

European-Finnish (FIN) AF: 0.0000991 AC: 1 AN: 10092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67068

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8
Mutation Taster		=122/78	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587779737; hg19: chr1-27023007;