dbSNP rs12685: ARID1A:c.*998T>C (chr1-26781754-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.51

Publications

18 publications found

Variant links:

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)

ARID1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6 link	c.*998T>C		3_prime_UTR_variant	Exon 20 of 20	ENST00000324856.13	NP_006006.3	O14497-1
ARID1A	NM_139135.4 link	c.*998T>C		3_prime_UTR_variant	Exon 20 of 20		NP_624361.1	O14497-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARID1A	ENST00000324856.13 link	c.*998T>C	3_prime_UTR_variant	Exon 20 of 20	1	NM_006015.6	ENSP00000320485.7	O14497-1
ARID1A	ENST00000850904.1 link	c.*998T>C	3_prime_UTR_variant	Exon 20 of 20			ENSP00000520984.1
ARID1A	ENST00000636219.1 link	c.*998T>C	3_prime_UTR_variant	Exon 19 of 19	5		ENSP00000489842.1	A0A1B0GTU5

Frequencies

GnomAD3 genomes

AF:

0.0574

AC:

8734

AN:

152210

Hom.:

323

Cov.:

show subpopulations

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.:

AF XY:

0.0588

AC XY:

2204

AN XY:

37460

show subpopulations

African (AFR)

AF:

0.0239

AC:

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:

AN:

11398

South Asian (SAS)

AF:

0.0313

AC:

AN:

702

European-Finnish (FIN)

AF:

0.0930

AC:

AN:

484

Middle Eastern (MID)

AF:

0.0569

AC:

AN:

492

European-Non Finnish (NFE)

AF:

0.0750

AC:

3752

AN:

50010

Other (OTH)

AF:

0.0563

AC:

381

AN:

6772

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

245

490

734

979

1224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0574

AC:

8741

AN:

152328

Hom.:

324

Cov.:

AF XY:

0.0570

AC XY:

4248

AN XY:

74482

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0799

AC:

5433

AN:

68032

Other (OTH)

AF:

0.0549

AC:

116

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

433

866

1300

1733

2166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over