NM_006015.6:c.2989-125A>G

Variant names:

• chr1-26767665-A-G
• rs34502618
• NM_006015.6:c.2989-125A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 -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 rank	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.2989-125A>G		intron_variant	Intron 10 of 19	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.2989-125A>G		intron_variant	Intron 10 of 19		NP_624361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.2989-125A>G		intron_variant	Intron 10 of 19	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

African (AFR) AF: 0.0782 AC: 1496 AN: 19126

American (AMR) AF: 0.0806 AC: 1515 AN: 18802

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 2372 AN: 15952

East Asian (EAS) AF: 0.0216 AC: 711 AN: 32956

South Asian (SAS) AF: 0.108 AC: 5728 AN: 52970

European-Finnish (FIN) AF: 0.155 AC: 5063 AN: 32632

Middle Eastern (MID) AF: 0.125 AC: 368 AN: 2936

European-Non Finnish (NFE) AF: 0.166 AC: 99641 AN: 601588

Other (OTH) AF: 0.138 AC: 5235 AN: 38016

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

African (AFR) AF: 0.0827 AC: 3438 AN: 41548

American (AMR) AF: 0.102 AC: 1558 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3470

East Asian (EAS) AF: 0.0356 AC: 185 AN: 5194

South Asian (SAS) AF: 0.102 AC: 491 AN: 4822

European-Finnish (FIN) AF: 0.160 AC: 1691 AN: 10572

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.168 AC: 11396 AN: 67996

Other (OTH) AF: 0.129 AC: 272 AN: 2110

Alfa AF: 0.144 Hom.: 263

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.70
PhyloP100		-0.48
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: rs34502618; hg19: chr1-27094156; COSMIC: COSV104411669;