1-26781754-T-C

Variant names:

• chr1-26781754-T-C
• rs12685
• NM_006015.6:c.*998T>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.*998T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.058 in 233,710 control chromosomes in the GnomAD database, including 488 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 (324 hom., cov: 32)
  • Exomes 𝑓: 0.059 (164 hom.)
• Consequence: ARID1A NM_006015.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 18 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=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0781 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006015.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1A	NM_006015.6	MANE Select	c.*998T>C		3_prime_UTR	Exon 20 of 20	NP_006006.3
	ARID1A	NM_139135.4		c.*998T>C		3_prime_UTR	Exon 20 of 20	NP_624361.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1A	ENST00000324856.13	TSL:1 MANE Select	c.*998T>C		3_prime_UTR	Exon 20 of 20	ENSP00000320485.7
	ARID1A	ENST00000850904.1		c.*998T>C		3_prime_UTR	Exon 20 of 20	ENSP00000520984.1
	ARID1A	ENST00000636219.1	TSL:5	c.*998T>C		3_prime_UTR	Exon 19 of 19	ENSP00000489842.1

Frequencies

GnomAD3 genomes AF: 0.0574 AC: 8734 AN: 152210 Hom.: 323 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0538

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.0486

Gnomad FIN AF: 0.0828

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0799

Gnomad OTH AF: 0.0550

GnomAD4 exome AF: 0.0590 AC: 4804 AN: 81382 Hom.: 164 Cov.: 0 AF XY: 0.0588 AC XY: 2204 AN XY: 37460

African (AFR) AF: 0.0239 AC: 93 AN: 3898

American (AMR) AF: 0.0512 AC: 128 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.0529 AC: 271 AN: 5126

East Asian (EAS) AF: 0.00737 AC: 84 AN: 11398

South Asian (SAS) AF: 0.0313 AC: 22 AN: 702

European-Finnish (FIN) AF: 0.0930 AC: 45 AN: 484

Middle Eastern (MID) AF: 0.0569 AC: 28 AN: 492

European-Non Finnish (NFE) AF: 0.0750 AC: 3752 AN: 50010

Other (OTH) AF: 0.0563 AC: 381 AN: 6772

GnomAD4 genome AF: 0.0574 AC: 8741 AN: 152328 Hom.: 324 Cov.: 32 AF XY: 0.0570 AC XY: 4248 AN XY: 74482

African (AFR) AF: 0.0216 AC: 899 AN: 41586

American (AMR) AF: 0.0537 AC: 821 AN: 15300

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

East Asian (EAS) AF: 0.0224 AC: 116 AN: 5190

South Asian (SAS) AF: 0.0489 AC: 236 AN: 4828

European-Finnish (FIN) AF: 0.0828 AC: 878 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0799 AC: 5433 AN: 68032

Other (OTH) AF: 0.0549 AC: 116 AN: 2114

Alfa AF: 0.0632 Hom.: 422

Bravo AF: 0.0532

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs12685; hg19: chr1-27108245;