6-157207063-C-T

Position:

chr6-157207063-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.6291C>T(p.Ile2097Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00937 in 1,614,160 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0095 ( 99 hom. )

Consequence

ARID1B
NM_001374828.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.33

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 6-157207063-C-T is Benign according to our data. Variant chr6-157207063-C-T is described in ClinVar as [Benign]. Clinvar id is 126336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-157207063-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.33 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00814 (1240/152270) while in subpopulation NFE AF= 0.0117 (794/68018). AF 95% confidence interval is 0.011. There are 10 homozygotes in gnomad4. There are 574 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1240 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1 linkuse as main transcript	c.6291C>T	p.Ile2097Ile	synonymous_variant	20/20	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.6291C>T	p.Ile2097Ile	synonymous_variant	20/20	2	NM_001374828.1	ENSP00000490491.2		Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes

AF:

0.00814

AC:

1239

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00936

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00933

Gnomad FIN

AF:

0.00981

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.00814

GnomAD3 exomes

AF:

0.00991

AC:

2489

AN:

251250

Hom.:

AF XY:

0.0106

AC XY:

1438

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00682

Gnomad ASJ exome

AF:

0.00586

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0135

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.00950

AC:

13881

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00980

AC XY:

7127

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00693

Gnomad4 ASJ exome

AF:

0.00620

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0132

Gnomad4 FIN exome

AF:

0.0114

Gnomad4 NFE exome

AF:

0.00983

Gnomad4 OTH exome

AF:

0.00932

GnomAD4 genome

AF:

0.00814

AC:

1240

AN:

152270

Hom.:

Cov.:

AF XY:

0.00771

AC XY:

574

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00934

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00955

Gnomad4 FIN

AF:

0.00981

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00882

Hom.:

Bravo

AF:

0.00783

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.0157

EpiControl

AF:

0.0140

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	ARID1B: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 15, 2020	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 23, 2015

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2016

This alteration is classified as 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. -

Coffin-Siris syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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