1-26696516-AGGCGGCGGCGGC-AGGC

Variant names:

• chr1-26696516-AGGCGGCGGC-A
• rs587779737
• NM_006015.6:c.120_128delGGCGGCGGC

Variant summary

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

The NM_006015.6(ARID1A):​c.120_128delGGCGGCGGC​(p.Ala41_Ala43del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000158 in 1,075,484 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: ARID1A NM_006015.6 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• 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 -2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_006015.6.
• BS2: High AC in GnomAdExome4 at 17 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.120_128delGGCGGCGGC	p.Ala41_Ala43del	disruptive_inframe_deletion	Exon 1 of 20	NP_006006.3
	ARID1A	NM_139135.4		c.120_128delGGCGGCGGC	p.Ala41_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.120_128delGGCGGCGGC	p.Ala41_Ala43del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000320485.7
	ARID1A	ENST00000850904.1		c.120_128delGGCGGCGGC	p.Ala41_Ala43del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000520984.1
	ARID1A	ENST00000457599.7	TSL:5	c.120_128delGGCGGCGGC	p.Ala41_Ala43del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000387636.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000158 AC: 17 AN: 1075484 Hom.: 0 AF XY: 0.0000118 AC XY: 6 AN XY: 510436

African (AFR) AF: 0.00 AC: 0 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: 0.0000185 AC: 17 AN: 918526

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8

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; COSMIC: COSV108137375; COSMIC: COSV108137375;