chr1-26696516-A-AGGCGGC

Position:

• chr1-26696516-A-AGGCGGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM4 BP6_Very_Strong BS2

The NM_006015.6(ARID1A):​c.123_128dupGGCGGC​(p.Ala42_Ala43dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000784 in 1,224,588 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000067 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000080 (0 hom.)
• Consequence: ARID1A NM_006015.6 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.712

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 Benign. Variant got -10 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_006015.6.
• BP6: Variant 1-26696516-A-AGGCGGC is Benign according to our data. Variant chr1-26696516-A-AGGCGGC is described in ClinVar as [Likely_benign]. Clinvar id is 1346038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.123_128dupGGCGGC	p.Ala42_Ala43dup	disruptive_inframe_insertion	1/20	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.123_128dupGGCGGC	p.Ala42_Ala43dup	disruptive_inframe_insertion	1/20		NP_624361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.123_128dupGGCGGC	p.Ala42_Ala43dup	disruptive_inframe_insertion	1/20	1	NM_006015.6	ENSP00000320485.7
ARID1A	ENST00000457599.6	c.123_128dupGGCGGC	p.Ala42_Ala43dup	disruptive_inframe_insertion	1/20	5		ENSP00000387636.2
ARID1A	ENST00000430799.7	c.-13+2909_-13+2914dupGGCGGC		intron_variant		5		ENSP00000390317.3
ARID1A	ENST00000637465.1	c.-13+426_-13+431dupGGCGGC		intron_variant		5		ENSP00000490650.1

Frequencies

GnomAD3 genomes AF: 0.0000671 AC: 10 AN: 149104 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000664

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: 0.000119

Gnomad OTH AF: 0.000488

GnomAD4 exome AF: 0.0000800 AC: 86 AN: 1075484 Hom.: 0 Cov.: 35 AF XY: 0.0000999 AC XY: 51 AN XY: 510436

Gnomad4 AFR exome AF: 0.0000450

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000395

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000472

Gnomad4 NFE exome AF: 0.0000871

Gnomad4 OTH exome AF: 0.0000702

GnomAD4 genome AF: 0.0000671 AC: 10 AN: 149104 Hom.: 0 Cov.: 31 AF XY: 0.0000687 AC XY: 5 AN XY: 72786

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000664

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000119

Gnomad4 OTH AF: 0.000488

Bravo AF: 0.0000793

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 16, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	ARID1A: BS1 -

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: rs587779737; hg19: chr1-27023007;