chr1-26696448-CCCGCCGCCG-C

Variant names:

• chr1-26696448-CCCGCCGCCG-C
• NM_006015.6:c.54_62delGCCGCCGCC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006015.6(ARID1A):​c.54_62delGCCGCCGCC​(p.Pro19_Pro21del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000878 in 1,138,724 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: ARID1A NM_006015.6 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.54_62delGCCGCCGCC	p.Pro19_Pro21del	disruptive_inframe_deletion	Exon 1 of 20	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.54_62delGCCGCCGCC	p.Pro19_Pro21del	disruptive_inframe_deletion	Exon 1 of 20		NP_624361.1
LOC124900417	XM_047439473.1	c.-52_-44delCGGCGGCGG		upstream_gene_variant			XP_047295429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.54_62delGCCGCCGCC	p.Pro19_Pro21del	disruptive_inframe_deletion	Exon 1 of 20	1	NM_006015.6	ENSP00000320485.7
ARID1A	ENST00000457599.6	c.54_62delGCCGCCGCC	p.Pro19_Pro21del	disruptive_inframe_deletion	Exon 1 of 20	5		ENSP00000387636.2
ARID1A	ENST00000430799.7	c.-13+2840_-13+2848delGCCGCCGCC		intron_variant	Intron 1 of 19	5		ENSP00000390317.3
ARID1A	ENST00000637465.1	c.-13+357_-13+365delGCCGCCGCC		intron_variant	Intron 1 of 2	5		ENSP00000490650.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.78e-7 AC: 1 AN: 1138724 Hom.: 0 AF XY: 0.00000181 AC XY: 1 AN XY: 552490

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: 0.0000262

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-27022939;