6-157184284-C-T

Position:

chr6-157184284-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001374828.1(ARID1B):c.3768C>T(p.Thr1256Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 1,614,130 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 12 hom. )

Consequence

ARID1B
NM_001374828.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.222

Variant links:

Genes affected

ARID1B (HGNC:18040): (AT-rich interaction domain 1B) This locus encodes an AT-rich DNA interacting domain-containing protein. The encoded protein is a component of the SWI/SNF chromatin remodeling complex and may play a role in cell-cycle activation. The protein encoded by this locus is similar to AT-rich interactive domain-containing protein 1A. These two proteins function as alternative, mutually exclusive ARID-subunits of the SWI/SNF complex. The associated complexes play opposing roles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ARID1B links:

ARID1B (HGNC:):

ARID1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 6-157184284-C-T is Benign according to our data. Variant chr6-157184284-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 434360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.222 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00303 (461/152300) while in subpopulation AMR AF= 0.0047 (72/15304). AF 95% confidence interval is 0.0039. There are 0 homozygotes in gnomad4. There are 218 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 461 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1 linkuse as main transcript	c.3768C>T	p.Thr1256Thr	synonymous_variant	13/20	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2 linkuse as main transcript	c.3768C>T	p.Thr1256Thr	synonymous_variant	13/20	2	NM_001374828.1	ENSP00000490491.2		Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes

AF:

0.00303

AC:

461

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00431

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00290

AC:

730

AN:

251374

Hom.:

AF XY:

0.00295

AC XY:

401

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.00724

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.00199

Gnomad NFE exome

AF:

0.00442

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00419

AC:

6118

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00405

AC XY:

2945

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.00597

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000696

Gnomad4 FIN exome

AF:

0.00202

Gnomad4 NFE exome

AF:

0.00489

Gnomad4 OTH exome

AF:

0.00409

GnomAD4 genome

AF:

0.00303

AC:

461

AN:

152300

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000986

Gnomad4 AMR

AF:

0.00470

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00431

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00454

Hom.:

Bravo

AF:

0.00300

EpiCase

AF:

0.00485

EpiControl

AF:

0.00403

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	ARID1B: BP4, BP7, BS1 -

Coffin-Siris syndrome 1

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 31, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 17, 2017

- -

ARID1B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 24, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2016

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.64

DANN

Benign

0.90

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