rs12743862

Variant names:

• chr1-26701730-A-G
• rs12743862
• NM_006015.6:c.1137+4190A>G

Variant summary

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

The NM_006015.6(ARID1A):​c.1137+4190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 152,220 control chromosomes in the GnomAD database, including 421 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 0.072 (421 hom., cov: 32)
• Consequence: ARID1A NM_006015.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.1137+4190A>G		intron_variant	Intron 1 of 19	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.1137+4190A>G		intron_variant	Intron 1 of 19		NP_624361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.1137+4190A>G		intron_variant	Intron 1 of 19	1	NM_006015.6	ENSP00000320485.7

Frequencies

GnomAD3 genomes AF: 0.0716 AC: 10884 AN: 152102 Hom.: 417 Cov.: 32

Gnomad AFR AF: 0.0701

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0602

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.0227

Gnomad SAS AF: 0.0491

Gnomad FIN AF: 0.0835

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.0651

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

GnomAD4 genome AF: 0.0717 AC: 10909 AN: 152220 Hom.: 421 Cov.: 32 AF XY: 0.0713 AC XY: 5307 AN XY: 74424

African (AFR) AF: 0.0705 AC: 2929 AN: 41524

American (AMR) AF: 0.0601 AC: 919 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 174 AN: 3470

East Asian (EAS) AF: 0.0226 AC: 117 AN: 5188

South Asian (SAS) AF: 0.0491 AC: 237 AN: 4822

European-Finnish (FIN) AF: 0.0835 AC: 885 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0800 AC: 5443 AN: 68006

Other (OTH) AF: 0.0649 AC: 137 AN: 2112

Alfa AF: 0.0718 Hom.: 501

Bravo AF: 0.0689

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.56
PhyloP100		0.61
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: rs12743862; hg19: chr1-27028221;