1-26696671-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006015.6(ARID1A):c.268A>G(p.Ser90Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,317,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S90R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

ARID1A
NM_006015.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 0.0260

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011024505).

BP6

Variant 1-26696671-A-G is Benign according to our data. Variant chr1-26696671-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 434314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1A	NM_006015.6 linkuse as main transcript	c.268A>G	p.Ser90Gly	missense_variant	1/20	ENST00000324856.13
ARID1A	NM_139135.4 linkuse as main transcript	c.268A>G	p.Ser90Gly	missense_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1A	ENST00000324856.13 linkuse as main transcript	c.268A>G	p.Ser90Gly	missense_variant	1/20	1	NM_006015.6		O14497-1
ARID1A	ENST00000457599.6 linkuse as main transcript	c.268A>G	p.Ser90Gly	missense_variant	1/20	5			O14497-2
ARID1A	ENST00000430799.7 linkuse as main transcript	c.-13+3054A>G		intron_variant		5		A2
ARID1A	ENST00000637465.1 linkuse as main transcript	c.-13+571A>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000741

AC:

AN:

148390

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000744

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000208

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000105

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000626

AC:

AN:

15966

Hom.:

AF XY:

0.000102

AC XY:

AN XY:

9766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000281

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000187

AC:

219

AN:

1169016

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

102

AN XY:

568764

show subpopulations

Gnomad4 AFR exome

AF:

0.000128

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000222

Gnomad4 SAS exome

AF:

0.000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000210

Gnomad4 OTH exome

AF:

0.0000428

GnomAD4 genome

AF:

0.0000741

AC:

AN:

148516

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

72578

show subpopulations

Gnomad4 AFR

AF:

0.0000742

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000208

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000105

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000102

ExAC

AF:

0.0000889

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 14

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
not provided, no classification provided	phenotyping only	GenomeConnect - Invitae Patient Insights Network	-	Variant interpreted as Uncertain significance and reported on 04-14-2021 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 02, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 12, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

Cadd

Benign

9.9

Dann

Benign

0.28

DEOGEN2

Benign

0.054

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.39

T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.89

N;N

REVEL

Benign

0.026

Sift

Benign

1.0

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.20

Loss of glycosylation at S90 (P = 0.0016);Loss of glycosylation at S90 (P = 0.0016);

MVP

0.14

MPC

0.48

ClinPred

0.036

GERP RS

-2.2

Varity_R

0.041

gMVP

0.081

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over