rs3734441

Positions:

• chr6-157084796-G-A
• chr6-157084796-G-C
• chr6-157084796-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001374828.1(ARID1B):​c.2382G>A​(p.Ala794=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,613,790 control chromosomes in the GnomAD database, including 219,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17741 hom., cov: 31)
  • Exomes 𝑓: 0.52 (202040 hom.)
• Consequence: ARID1B NM_001374828.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.618

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-157084796-G-A is Benign according to our data. Variant chr6-157084796-G-A is described in ClinVar as [Benign]. Clinvar id is 126320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-157084796-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.618 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.2382G>A	p.Ala794=	synonymous_variant	5/20	ENST00000636930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.2382G>A	p.Ala794=	synonymous_variant	5/20	2	NM_001374828.1	A2

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71824 AN: 151786 Hom.: 17738 Cov.: 31

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.499

GnomAD3 exomes AF: 0.523 AC: 131459 AN: 251256 Hom.: 35194 AF XY: 0.527 AC XY: 71548 AN XY: 135798

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.610

Gnomad ASJ exome AF: 0.608

Gnomad EAS exome AF: 0.550

Gnomad SAS exome AF: 0.566

Gnomad FIN exome AF: 0.389

Gnomad NFE exome AF: 0.527

Gnomad OTH exome AF: 0.521

GnomAD4 exome AF: 0.523 AC: 764659 AN: 1461886 Hom.: 202040 Cov.: 80 AF XY: 0.525 AC XY: 381655 AN XY: 727244

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.603

Gnomad4 ASJ exome AF: 0.606

Gnomad4 EAS exome AF: 0.571

Gnomad4 SAS exome AF: 0.571

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.520

GnomAD4 genome AF: 0.473 AC: 71858 AN: 151904 Hom.: 17741 Cov.: 31 AF XY: 0.472 AC XY: 35011 AN XY: 74246

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.499

Alfa AF: 0.526 Hom.: 39031

Bravo AF: 0.479

Asia WGS AF: 0.526 AC: 1831 AN: 3478

EpiCase AF: 0.539

EpiControl AF: 0.541

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 25, 2013	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 13, 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 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.60
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs3734441; hg19: chr6-157405930; COSMIC: COSV51659621;