1-26696448-CCCG-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_006015.6(ARID1A):c.60_62del(p.Pro21del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,268,634 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (0 hom.)
• Consequence: ARID1A NM_006015.6 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.288

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]

LOC124900417 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 1-26696448-CCCG-C is Benign according to our data. Variant chr1-26696448-CCCG-C is described in ClinVar as [Likely_benign]. Clinvar id is 770843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00131 (1468/1121628) while in subpopulation SAS AF= 0.00878 (323/36800). AF 95% confidence interval is 0.00799. There are 0 homozygotes in gnomad4_exome. There are 933 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome at 185 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1A	NM_006015.6	c.60_62del	p.Pro21del	inframe_deletion	1/20	ENST00000324856.13
ARID1A	NM_139135.4	c.60_62del	p.Pro21del	inframe_deletion	1/20
LOC124900417	XM_047439473.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1A	ENST00000324856.13	c.60_62del	p.Pro21del	inframe_deletion	1/20	1	NM_006015.6
ARID1A	ENST00000457599.6	c.60_62del	p.Pro21del	inframe_deletion	1/20	5
ARID1A	ENST00000430799.7	c.-13+2846_-13+2848del		intron_variant		5		A2
ARID1A	ENST00000637465.1	c.-13+363_-13+365del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000204 AC: 3 AN: 147006 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000670

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

GnomAD3 exomes AF: 0.0121 AC: 185 AN: 15288 Hom.: 0 AF XY: 0.0123 AC XY: 114 AN XY: 9294

Gnomad AFR exome AF: 0.00847

Gnomad AMR exome AF: 0.0121

Gnomad ASJ exome AF: 0.0123

Gnomad EAS exome AF: 0.00575

Gnomad SAS exome AF: 0.0125

Gnomad FIN exome AF: 0.00998

Gnomad NFE exome AF: 0.0126

Gnomad OTH exome AF: 0.0127

GnomAD4 exome AF: 0.00131 AC: 1468 AN: 1121628 Hom.: 0 AF XY: 0.00172 AC XY: 933 AN XY: 543258

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00489

Gnomad4 ASJ exome AF: 0.00291

Gnomad4 EAS exome AF: 0.00135

Gnomad4 SAS exome AF: 0.00878

Gnomad4 FIN exome AF: 0.00243

Gnomad4 NFE exome AF: 0.000907

Gnomad4 OTH exome AF: 0.00167

GnomAD4 genome AF: 0.0000204 AC: 3 AN: 147006 Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 1 AN XY: 71860

Gnomad4 AFR AF: 0.0000249

Gnomad4 AMR AF: 0.0000670

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000151

Gnomad4 OTH AF: 0.00

Asia WGS AF: 0.00313 AC: 10 AN: 3214

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Sep 12, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 19, 2020	- -

ARID1A-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs748085214; hg19: chr1-27022939;