1-26696649-TGGCGGC-TGGCGGCGGCGGC

Variant names:

• chr1-26696649-T-TGGCGGC
• rs1015322780
• NM_006015.6:c.255_260dupCGGCGG

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM4 BP6 BS2

The NM_006015.6(ARID1A):​c.255_260dupCGGCGG​(p.Gly86_Gly87dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000921 in 1,303,402 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G87G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000089 (0 hom.)
• Consequence: ARID1A NM_006015.6 disruptive_inframe_insertion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 1.67

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 Likely_benign. Variant got -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_006015.6.
• BP6: Variant 1-26696649-T-TGGCGGC is Benign according to our data. Variant chr1-26696649-T-TGGCGGC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434330.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
• BS2: High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.255_260dupCGGCGG	p.Gly86_Gly87dup	disruptive_inframe_insertion	Exon 1 of 20	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.255_260dupCGGCGG	p.Gly86_Gly87dup	disruptive_inframe_insertion	Exon 1 of 20		NP_624361.1
LOC124900417	XM_047439473.1	c.-250_-245dupGCCGCC		upstream_gene_variant			XP_047295429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.255_260dupCGGCGG	p.Gly86_Gly87dup	disruptive_inframe_insertion	Exon 1 of 20	1	NM_006015.6	ENSP00000320485.7
ARID1A	ENST00000457599.6	c.255_260dupCGGCGG	p.Gly86_Gly87dup	disruptive_inframe_insertion	Exon 1 of 20	5		ENSP00000387636.2
ARID1A	ENST00000430799.7	c.-13+3041_-13+3046dupCGGCGG		intron_variant	Intron 1 of 19	5		ENSP00000390317.3
ARID1A	ENST00000637465.1	c.-13+558_-13+563dupCGGCGG		intron_variant	Intron 1 of 2	5		ENSP00000490650.1

Frequencies

GnomAD3 genomes AF: 0.000116 AC: 17 AN: 146546 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000672

Gnomad ASJ AF: 0.00380

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000676

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000890 AC: 103 AN: 1156856 Hom.: 0 Cov.: 35 AF XY: 0.0000873 AC XY: 49 AN XY: 561124

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00349

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000182

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000352

Gnomad4 OTH exome AF: 0.000194

GnomAD4 genome AF: 0.000116 AC: 17 AN: 146546 Hom.: 0 Cov.: 32 AF XY: 0.000168 AC XY: 12 AN XY: 71476

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000672

Gnomad4 ASJ AF: 0.00380

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000676

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000159

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Sep 21, 2015

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ARID1A-related disorder Benign:1

Aug 10, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

not provided Benign:1

Oct 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs1015322780; hg19: chr1-27023140;