1-26696875-C-T

Position:

chr1-26696875-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006015.6(ARID1A):c.472C>T(p.Pro158Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,360,252 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P158P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

ARID1A
NM_006015.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.11

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060768723).

BP6

Variant 1-26696875-C-T is Benign according to our data. Variant chr1-26696875-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 376870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00086 (130/151162) while in subpopulation NFE AF= 0.00161 (109/67650). AF 95% confidence interval is 0.00137. There are 0 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 130 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1A	NM_006015.6 linkuse as main transcript	c.472C>T	p.Pro158Ser	missense_variant	1/20	ENST00000324856.13	NP_006006.3	O14497-1
ARID1A	NM_139135.4 linkuse as main transcript	c.472C>T	p.Pro158Ser	missense_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.472C>T	p.Pro158Ser	missense_variant	1/20	1	NM_006015.6	ENSP00000320485.7	O14497-1
ARID1A	ENST00000457599.6 linkuse as main transcript	c.472C>T	p.Pro158Ser	missense_variant	1/20	5		ENSP00000387636.2	O14497-2
ARID1A	ENST00000430799.7 linkuse as main transcript	c.-13+3258C>T		intron_variant		5		ENSP00000390317.3	H0Y488
ARID1A	ENST00000637465.1 linkuse as main transcript	c.-13+775C>T		intron_variant		5		ENSP00000490650.1	A0A1B0GVT5

Frequencies

GnomAD3 genomes

AF:

0.000867

AC:

131

AN:

151050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000526

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000837

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00161

Gnomad OTH

AF:

0.000482

GnomAD3 exomes

AF:

0.000699

AC:

AN:

18610

Hom.:

AF XY:

0.000295

AC XY:

AN XY:

10174

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:

0.00

Gnomad FIN exome

AF:

0.000248

Gnomad NFE exome

AF:

0.00136

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00143

AC:

1733

AN:

1209090

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

803

AN XY:

585942

show subpopulations

Gnomad4 AFR exome

AF:

0.000291

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000210

Gnomad4 FIN exome

AF:

0.000276

Gnomad4 NFE exome

AF:

0.00167

Gnomad4 OTH exome

AF:

0.000978

GnomAD4 genome

AF:

0.000860

AC:

130

AN:

151162

Hom.:

Cov.:

AF XY:

0.000691

AC XY:

AN XY:

73830

show subpopulations

Gnomad4 AFR

AF:

0.000218

Gnomad4 AMR

AF:

0.000526

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000628

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00161

Gnomad4 OTH

AF:

0.000477

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.000797

ExAC

AF:

0.000473

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	ARID1A: BS1 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jul 15, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 21, 2021

- -

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

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.58

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.70

T;T

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.0061

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.97

L;L

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.80

N;N

REVEL

Benign

0.074

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.53

T;T

Polyphen

0.0

B;B

Vest4

0.17

MVP

0.22

MPC

0.52

ClinPred

0.21

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.27

gMVP

0.34

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