rs34502618

Positions:

• chr1-26767665-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006015.6(ARID1A):​c.2989-125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 967,190 control chromosomes in the GnomAD database, including 11,524 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1448 hom., cov: 32)
  • Exomes 𝑓: 0.15 (10076 hom.)
• Consequence: ARID1A NM_006015.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.476

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-26767665-A-G is Benign according to our data. Variant chr1-26767665-A-G is described in ClinVar as [Benign]. Clinvar id is 1297871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.2989-125A>G		intron_variant		ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.2989-125A>G		intron_variant			NP_624361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.2989-125A>G		intron_variant		1	NM_006015.6	ENSP00000320485.7

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19622 AN: 152094 Hom.: 1439 Cov.: 32

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0357

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.150 AC: 122129 AN: 814978 Hom.: 10076 AF XY: 0.148 AC XY: 60697 AN XY: 410400

Gnomad4 AFR exome AF: 0.0782

Gnomad4 AMR exome AF: 0.0806

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.0216

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.129 AC: 19656 AN: 152212 Hom.: 1448 Cov.: 32 AF XY: 0.127 AC XY: 9446 AN XY: 74432

Gnomad4 AFR AF: 0.0827

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0356

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.129

Alfa AF: 0.146 Hom.: 262

Bravo AF: 0.121

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.70

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: rs34502618; hg19: chr1-27094156; COSMIC: COSV104411669; COSMIC: COSV104411669;