1-26696885-TCGCCGCCGC-TCGC

Variant names:

• chr1-26696885-TCGCCGC-T
• rs759913677
• NM_006015.6:c.489_494delCGCCGC

Variant summary

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

The NM_006015.6(ARID1A):​c.489_494delCGCCGC​(p.Ala164_Ala165del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000512 in 1,348,618 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A163A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000052 (0 hom.)
• Consequence: ARID1A NM_006015.6 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02
• Publications: 1 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: ClinGen, Orphanet
• intellectual disability, autosomal dominant 14

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P

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 GnomAd4 at 6 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1A	NM_006015.6	MANE Select	c.489_494delCGCCGC	p.Ala164_Ala165del	disruptive_inframe_deletion	Exon 1 of 20	NP_006006.3
	ARID1A	NM_139135.4		c.489_494delCGCCGC	p.Ala164_Ala165del	disruptive_inframe_deletion	Exon 1 of 20	NP_624361.1	O14497-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1A	ENST00000324856.13	TSL:1 MANE Select	c.489_494delCGCCGC	p.Ala164_Ala165del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000320485.7	O14497-1
	ARID1A	ENST00000850904.1		c.489_494delCGCCGC	p.Ala164_Ala165del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000520984.1	A0ABJ7H312
	ARID1A	ENST00000457599.7	TSL:5	c.489_494delCGCCGC	p.Ala164_Ala165del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000387636.2	O14497-2

Frequencies

GnomAD3 genomes AF: 0.0000411 AC: 6 AN: 145868 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000764

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000671

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000223

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

GnomAD2 exomes AF: 0.0000420 AC: 1 AN: 23828 AF XY: 0.0000758

Gnomad AFR exome AF: 0.000954

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: 0.0000524 AC: 63 AN: 1202618 Hom.: 0 AF XY: 0.0000600 AC XY: 35 AN XY: 583276

African (AFR) AF: 0.000126 AC: 3 AN: 23872

American (AMR) AF: 0.000105 AC: 1 AN: 9544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15920

East Asian (EAS) AF: 0.0000729 AC: 2 AN: 27428

South Asian (SAS) AF: 0.0000211 AC: 1 AN: 47436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4700

European-Non Finnish (NFE) AF: 0.0000548 AC: 54 AN: 985418

Other (OTH) AF: 0.0000414 AC: 2 AN: 48288

GnomAD4 genome AF: 0.0000411 AC: 6 AN: 146000 Hom.: 0 Cov.: 32 AF XY: 0.0000421 AC XY: 3 AN XY: 71308

African (AFR) AF: 0.0000762 AC: 3 AN: 39370

American (AMR) AF: 0.0000671 AC: 1 AN: 14910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.000223 AC: 1 AN: 4478

South Asian (SAS) AF: 0.00 AC: 0 AN: 4372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66152

Other (OTH) AF: 0.00 AC: 0 AN: 2036

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

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		3.0
Mutation Taster		=117/83	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs759913677; hg19: chr1-27023376;