1-26697510-CG-CGG

Variant names:

• chr1-26697510-C-CG
• NM_006015.6:c.1113dupG

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 8P and 4B. PVS1 BS2

The NM_006015.6(ARID1A):​c.1113dupG​(p.Gln372AlafsTer28) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,252,600 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as other (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: ARID1A NM_006015.6 frameshift
• Clinical Significance: - - O:1
• Conservation: PhyloP100: 1.13

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 Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.1113dupG	p.Gln372AlafsTer28	frameshift_variant	Exon 1 of 20	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.1113dupG	p.Gln372AlafsTer28	frameshift_variant	Exon 1 of 20		NP_624361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.1113dupG	p.Gln372AlafsTer28	frameshift_variant	Exon 1 of 20	1	NM_006015.6	ENSP00000320485.7
ARID1A	ENST00000457599.6	c.1113dupG	p.Gln372AlafsTer28	frameshift_variant	Exon 1 of 20	5		ENSP00000387636.2
ARID1A	ENST00000430799.7	c.-13+3899dupG		intron_variant	Intron 1 of 19	5		ENSP00000390317.3
ARID1A	ENST00000637465.1	c.-13+1416dupG		intron_variant	Intron 1 of 2	5		ENSP00000490650.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000104 AC: 13 AN: 1252600 Hom.: 0 Cov.: 35 AF XY: 0.0000146 AC XY: 9 AN XY: 615460

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000132

Gnomad4 ASJ exome AF: 0.0000501

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000330

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000785

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: -

Submissions summary: Other:1

Revision: -

Submissions by phenotype

Neoplasm Other:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: -

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-27024001;