6-157167191-C-T

Position:

chr6-157167191-C-T

Variant summary

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

The NM_001374828.1(ARID1B):c.3235+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00491 in 1,603,540 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0050 ( 25 hom. )

Consequence

ARID1B
NM_001374828.1 splice_region, intron

Scores

Splicing: ADA: 0.00007175

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.372

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 6-157167191-C-T is Benign according to our data. Variant chr6-157167191-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 210280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-157167191-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00393 (599/152314) while in subpopulation NFE AF= 0.00651 (443/68026). AF 95% confidence interval is 0.00601. There are 2 homozygotes in gnomad4. There are 283 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 599 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1 linkuse as main transcript	c.3235+6C>T		splice_region_variant, intron_variant		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.3235+6C>T		splice_region_variant, intron_variant		2	NM_001374828.1	ENSP00000490491.2		Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes

AF:

0.00393

AC:

598

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00651

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00383

AC:

923

AN:

241144

Hom.:

AF XY:

0.00417

AC XY:

547

AN XY:

131080

show subpopulations

Gnomad AFR exome

AF:

0.000873

Gnomad AMR exome

AF:

0.00376

Gnomad ASJ exome

AF:

0.00412

Gnomad EAS exome

AF:

0.000166

Gnomad SAS exome

AF:

0.00250

Gnomad FIN exome

AF:

0.000540

Gnomad NFE exome

AF:

0.00555

Gnomad OTH exome

AF:

0.00536

GnomAD4 exome

AF:

0.00502

AC:

7278

AN:

1451226

Hom.:

Cov.:

AF XY:

0.00504

AC XY:

3641

AN XY:

722438

show subpopulations

Gnomad4 AFR exome

AF:

0.000689

Gnomad4 AMR exome

AF:

0.00396

Gnomad4 ASJ exome

AF:

0.00460

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00263

Gnomad4 FIN exome

AF:

0.000626

Gnomad4 NFE exome

AF:

0.00570

Gnomad4 OTH exome

AF:

0.00518

GnomAD4 genome

AF:

0.00393

AC:

599

AN:

152314

Hom.:

Cov.:

AF XY:

0.00380

AC XY:

283

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000986

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00651

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00578

Hom.:

Bravo

AF:

0.00411

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00772

EpiControl

AF:

0.00729

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:8

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 31, 2019	This variant is associated with the following publications: (PMID: 22405089) -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 11, 2016	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	ARID1B: BP4, BS1, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 22, 2016

- -

ARID1B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 18, 2022

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). -

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

-0.76

CADD

Benign

9.8

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000072

dbscSNV1_RF

Benign

0.0040

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