rs12685

Positions:

• chr1-26781754-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.*998T>C		3_prime_UTR_variant	20/20	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.*998T>C		3_prime_UTR_variant	20/20		NP_624361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.*998T>C		3_prime_UTR_variant	20/20	1	NM_006015.6	ENSP00000320485
ARID1A	ENST00000636219.1	c.*998T>C		3_prime_UTR_variant	19/19	5		ENSP00000489842

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

Gnomad4 AFR exome AF: 0.0239

Gnomad4 AMR exome AF: 0.0512

Gnomad4 ASJ exome AF: 0.0529

Gnomad4 EAS exome AF: 0.00737

Gnomad4 SAS exome AF: 0.0313

Gnomad4 FIN exome AF: 0.0930

Gnomad4 NFE exome AF: 0.0750

Gnomad4 OTH exome AF: 0.0563

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

Gnomad4 AFR AF: 0.0216

Gnomad4 AMR AF: 0.0537

Gnomad4 ASJ AF: 0.0502

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.0489

Gnomad4 FIN AF: 0.0828

Gnomad4 NFE AF: 0.0799

Gnomad4 OTH AF: 0.0549

Alfa AF: 0.0649 Hom.: 346

Bravo AF: 0.0532

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs12685; hg19: chr1-27108245;