rs747438636

chr6-156778909-GAGGAGC-Gchr6-156778909-GAGGAGC-GAGGAGCAGGAGC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3 BP6 BS2

The NM_001374828.1(ARID1B):c.1241_1246del(p.Ala414_Gly415del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000909 in 1,352,964 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000084 (0 hom.)
• Consequence: ARID1B NM_001374828.1 inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:4
• Conservation: PhyloP100: 1.80

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 Likely_benign. Variant got -6 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778909-GAGGAGC-G is Benign according to our data. Variant chr6-156778909-GAGGAGC-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434375.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=1}.
• BS2: High AC in GnomAd at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.1241_1246del	p.Ala414_Gly415del	inframe_deletion	1/20	ENST00000636930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.1241_1246del	p.Ala414_Gly415del	inframe_deletion	1/20	2	NM_001374828.1	A2

Frequencies

GnomAD3 genomes AF: 0.000150 AC: 22 AN: 147044 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000270

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000432

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000205

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000602

Gnomad OTH AF: 0.000495

GnomAD3 exomes AF: 0.0000421 AC: 1 AN: 23744 Hom.: 0 AF XY: 0.0000696 AC XY: 1 AN XY: 14358

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: 0.00

Gnomad NFE exome AF: 0.000137

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000838 AC: 101 AN: 1205820 Hom.: 0 AF XY: 0.0000798 AC XY: 47 AN XY: 588802

Gnomad4 AFR exome AF: 0.000337

Gnomad4 AMR exome AF: 0.000432

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000819

Gnomad4 SAS exome AF: 0.0000419

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000798

Gnomad4 OTH exome AF: 0.000102

GnomAD4 genome AF: 0.000150 AC: 22 AN: 147144 Hom.: 0 Cov.: 29 AF XY: 0.000195 AC XY: 14 AN XY: 71844

Gnomad4 AFR AF: 0.000224

Gnomad4 AMR AF: 0.000270

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000433

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000205

Gnomad4 NFE AF: 0.0000602

Gnomad4 OTH AF: 0.000489

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:4

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Nov 17, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 06, 2021	- -

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 06, 2016

- -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2017

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. -

ARID1B-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 16, 2022

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

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs747438636; hg19: chr6-157100043;