GeneBe

rs748085214

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.57

Publications

0 publications found
Variant links:
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]
ARID1A Gene-Disease associations (from GenCC):
  • Coffin-Siris syndrome
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
  • intellectual disability, autosomal dominant 14
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_006015.6

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARID1ANM_006015.6 linkc.54_62delGCCGCCGCC p.Pro19_Pro21del disruptive_inframe_deletion Exon 1 of 20 ENST00000324856.13 NP_006006.3 O14497-1
ARID1ANM_139135.4 linkc.54_62delGCCGCCGCC p.Pro19_Pro21del disruptive_inframe_deletion Exon 1 of 20 NP_624361.1 O14497-2
LOC124900417XM_047439473.1 linkc.-52_-44delCGGCGGCGG upstream_gene_variant XP_047295429.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARID1AENST00000324856.13 linkc.54_62delGCCGCCGCC p.Pro19_Pro21del disruptive_inframe_deletion Exon 1 of 20 1 NM_006015.6 ENSP00000320485.7 O14497-1

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
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
23120
American (AMR)
AF:
0.00
AC:
0
AN:
11632
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
15874
East Asian (EAS)
AF:
0.00
AC:
0
AN:
25812
South Asian (SAS)
AF:
0.0000262
AC:
1
AN:
38202
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
23842
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3086
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
951960
Other (OTH)
AF:
0.00
AC:
0
AN:
45196
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.6

Splicing

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

Publications

Other links and lift over

dbSNP: rs748085214; hg19: chr1-27022939; API