1-26696721-C-T

Position:

chr1-26696721-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006015.6(ARID1A):c.318C>T(p.Asn106Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,370,886 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 7 hom. )

Consequence

ARID1A
NM_006015.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0430

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 1-26696721-C-T is Benign according to our data. Variant chr1-26696721-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 434315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.043 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00184 (278/150892) while in subpopulation NFE AF= 0.0032 (216/67558). AF 95% confidence interval is 0.00285. There are 0 homozygotes in gnomad4. There are 113 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 278 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1A	NM_006015.6 linkuse as main transcript	c.318C>T	p.Asn106Asn	synonymous_variant	1/20	ENST00000324856.13	NP_006006.3	O14497-1
ARID1A	NM_139135.4 linkuse as main transcript	c.318C>T	p.Asn106Asn	synonymous_variant	1/20		NP_624361.1	O14497-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARID1A	ENST00000324856.13 linkuse as main transcript	c.318C>T	p.Asn106Asn	synonymous_variant	1/20	1	NM_006015.6	ENSP00000320485.7	O14497-1
ARID1A	ENST00000457599.6 linkuse as main transcript	c.318C>T	p.Asn106Asn	synonymous_variant	1/20	5		ENSP00000387636.2	O14497-2
ARID1A	ENST00000430799.7 linkuse as main transcript	c.-13+3104C>T		intron_variant		5		ENSP00000390317.3	H0Y488
ARID1A	ENST00000637465.1 linkuse as main transcript	c.-13+621C>T		intron_variant		5		ENSP00000490650.1	A0A1B0GVT5

Frequencies

GnomAD3 genomes

AF:

0.00184

AC:

278

AN:

150784

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00132

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000289

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00320

Gnomad OTH

AF:

0.000965

GnomAD3 exomes

AF:

0.00144

AC:

AN:

29208

Hom.:

AF XY:

0.00135

AC XY:

AN XY:

17780

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00759

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000377

Gnomad NFE exome

AF:

0.00199

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

AF:

0.00304

AC:

3709

AN:

1219994

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

1800

AN XY:

597530

show subpopulations

Gnomad4 AFR exome

AF:

0.000208

Gnomad4 AMR exome

AF:

0.00146

Gnomad4 ASJ exome

AF:

0.00715

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000558

Gnomad4 FIN exome

AF:

0.000602

Gnomad4 NFE exome

AF:

0.00343

Gnomad4 OTH exome

AF:

0.00231

GnomAD4 genome

AF:

0.00184

AC:

278

AN:

150892

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

113

AN XY:

73738

show subpopulations

Gnomad4 AFR

AF:

0.000486

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000289

Gnomad4 NFE

AF:

0.00320

Gnomad4 OTH

AF:

0.000954

Alfa

AF:

0.00254

Hom.:

Bravo

AF:

0.00208

Asia WGS

AF:

0.00118

AC:

AN:

3416

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	ARID1A: BP4, BP7, BS1 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 11, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 27, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 21, 2020

- -

Intellectual disability, autosomal dominant 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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