rs12731749

Variant names:

• chr1-26759071-T-C
• rs12731749
• NM_006015.6:c.1921-1785T>C

Variant summary

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

The NM_006015.6(ARID1A):​c.1921-1785T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 152,176 control chromosomes in the GnomAD database, including 320 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 0.057 (320 hom., cov: 32)
• Consequence: ARID1A NM_006015.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.078 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.1921-1785T>C		intron_variant	Intron 4 of 19	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.1921-1785T>C		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.1921-1785T>C		intron_variant	Intron 4 of 19	1	NM_006015.6	ENSP00000320485.7

Frequencies

GnomAD3 genomes AF: 0.0568 AC: 8635 AN: 152058 Hom.: 319 Cov.: 32

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0538

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0798

Gnomad OTH AF: 0.0540

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

GnomAD4 genome AF: 0.0568 AC: 8641 AN: 152176 Hom.: 320 Cov.: 32 AF XY: 0.0565 AC XY: 4199 AN XY: 74382

African (AFR) AF: 0.0198 AC: 824 AN: 41516

American (AMR) AF: 0.0537 AC: 821 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 174 AN: 3472

East Asian (EAS) AF: 0.0195 AC: 101 AN: 5184

South Asian (SAS) AF: 0.0484 AC: 233 AN: 4818

European-Finnish (FIN) AF: 0.0834 AC: 882 AN: 10580

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

European-Non Finnish (NFE) AF: 0.0798 AC: 5424 AN: 67998

Other (OTH) AF: 0.0539 AC: 114 AN: 2114

Alfa AF: 0.0627 Hom.: 48

Bravo AF: 0.0525

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12731749; hg19: chr1-27085562;