1-26696885-TCGCCGCCGC-TCGCCGCCGCCGCCGC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4 BS2

The NM_006015.6(ARID1A):c.489_494dup(p.Ala166_Ala167dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,348,488 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V161V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: ARID1A NM_006015.6 inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.849

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_006015.6.
• BS2: High AC in GnomAd at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1A	NM_006015.6	c.489_494dup	p.Ala166_Ala167dup	inframe_insertion	1/20	ENST00000324856.13
ARID1A	NM_139135.4	c.489_494dup	p.Ala166_Ala167dup	inframe_insertion	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1A	ENST00000324856.13	c.489_494dup	p.Ala166_Ala167dup	inframe_insertion	1/20	1	NM_006015.6
ARID1A	ENST00000457599.6	c.489_494dup	p.Ala166_Ala167dup	inframe_insertion	1/20	5
ARID1A	ENST00000430799.7	c.-13+3275_-13+3280dup		intron_variant		5		A2
ARID1A	ENST00000637465.1	c.-13+792_-13+797dup		intron_variant		5

Frequencies

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

Gnomad AFR AF: 0.0000255

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: 0.000197

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000453

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000191 AC: 23 AN: 1202620 Hom.: 0 Cov.: 35 AF XY: 0.0000206 AC XY: 12 AN XY: 583278

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000211

Gnomad4 FIN exome AF: 0.0000750

Gnomad4 NFE exome AF: 0.0000173

Gnomad4 OTH exome AF: 0.0000414

GnomAD4 genome AF: 0.0000411 AC: 6 AN: 145868 Hom.: 0 Cov.: 32 AF XY: 0.0000281 AC XY: 2 AN XY: 71176

Gnomad4 AFR AF: 0.0000255

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000197

Gnomad4 NFE AF: 0.0000453

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs759913677; hg19: chr1-27023376;