rs12735646

Variant names:

• chr1-26751875-G-A
• rs12735646
• NM_006015.6:c.1921-8981G>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.1921-8981G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 152,162 control chromosomes in the GnomAD database, including 327 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 0.060 (327 hom., cov: 32)
• Consequence: ARID1A NM_006015.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 13 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.1921-8981G>A		intron_variant	Intron 4 of 19	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.1921-8981G>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.1921-8981G>A		intron_variant	Intron 4 of 19	1	NM_006015.6	ENSP00000320485.7

Frequencies

GnomAD3 genomes AF: 0.0598 AC: 9099 AN: 152044 Hom.: 326 Cov.: 32

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0548

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.0832

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.0559

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

GnomAD4 genome AF: 0.0598 AC: 9104 AN: 152162 Hom.: 327 Cov.: 32 AF XY: 0.0593 AC XY: 4412 AN XY: 74404

African (AFR) AF: 0.0302 AC: 1254 AN: 41512

American (AMR) AF: 0.0547 AC: 836 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0502 AC: 174 AN: 3468

East Asian (EAS) AF: 0.0230 AC: 119 AN: 5184

South Asian (SAS) AF: 0.0487 AC: 235 AN: 4824

European-Finnish (FIN) AF: 0.0832 AC: 880 AN: 10576

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0797 AC: 5420 AN: 67990

Other (OTH) AF: 0.0558 AC: 118 AN: 2116

Alfa AF: 0.0651 Hom.: 61

Bravo AF: 0.0560

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.6
DANN	Benign	0.48
PhyloP100		0.14
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: rs12735646; hg19: chr1-27078366;