NM_006015.6:c.1920+8134G>A

Variant names:

• chr1-26740926-G-A
• rs11247594
• NM_006015.6:c.1920+8134G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006015.6(ARID1A):​c.1920+8134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,030 control chromosomes in the GnomAD database, including 9,930 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (9930 hom., cov: 31)
• Consequence: ARID1A NM_006015.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 11 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.1920+8134G>A		intron_variant	Intron 4 of 19	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.1920+8134G>A		intron_variant	Intron 4 of 19		NP_624361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.1920+8134G>A		intron_variant	Intron 4 of 19	1	NM_006015.6	ENSP00000320485.7

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48540 AN: 151912 Hom.: 9915 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.348

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.320 AC: 48581 AN: 152030 Hom.: 9930 Cov.: 31 AF XY: 0.329 AC XY: 24420 AN XY: 74308

African (AFR) AF: 0.385 AC: 15924 AN: 41406

American (AMR) AF: 0.497 AC: 7596 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 762 AN: 3470

East Asian (EAS) AF: 0.929 AC: 4812 AN: 5178

South Asian (SAS) AF: 0.498 AC: 2399 AN: 4814

European-Finnish (FIN) AF: 0.198 AC: 2092 AN: 10570

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13946 AN: 67990

Other (OTH) AF: 0.354 AC: 750 AN: 2116

Alfa AF: 0.247 Hom.: 8652

Bravo AF: 0.347

Asia WGS AF: 0.689 AC: 2398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.33
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11247594; hg19: chr1-27067417;