6-156778982-AGGCGGCGGC-AGGCGGC

Position:

• chr6-156778982-AGGCGGCGGC-AGGCGGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3 BP6 BS1 BS2

The NM_001374828.1(ARID1B):​c.1318_1320del​(p.Gly440del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000634 in 1,261,192 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00048 (1 hom.)
• Consequence: ARID1B NM_001374828.1 inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:6
• Conservation: PhyloP100: 0.931

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 -10 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778982-AGGC-A is Benign according to our data. Variant chr6-156778982-AGGC-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210266.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1, Benign=1}. Variant chr6-156778982-AGGC-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00185 (254/137394) while in subpopulation AFR AF= 0.00593 (218/36754). AF 95% confidence interval is 0.00529. There are 0 homozygotes in gnomad4. There are 114 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 254 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.1318_1320del	p.Gly440del	inframe_deletion	1/20	ENST00000636930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.1318_1320del	p.Gly440del	inframe_deletion	1/20	2	NM_001374828.1	A2

Frequencies

GnomAD3 genomes AF: 0.00184 AC: 252 AN: 137288 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00589

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000842

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00187

Gnomad SAS AF: 0.000240

Gnomad FIN AF: 0.000335

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000127

Gnomad OTH AF: 0.00213

GnomAD3 exomes AF: 0.00159 AC: 3 AN: 1892 Hom.: 0 AF XY: 0.00175 AC XY: 2 AN XY: 1144

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00952

Gnomad FIN exome AF: 0.00120

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000485 AC: 545 AN: 1123798 Hom.: 1 AF XY: 0.000486 AC XY: 263 AN XY: 541002

Gnomad4 AFR exome AF: 0.00451

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.000139

Gnomad4 EAS exome AF: 0.00694

Gnomad4 SAS exome AF: 0.00105

Gnomad4 FIN exome AF: 0.000365

Gnomad4 NFE exome AF: 0.000183

Gnomad4 OTH exome AF: 0.000685

GnomAD4 genome AF: 0.00185 AC: 254 AN: 137394 Hom.: 0 Cov.: 29 AF XY: 0.00169 AC XY: 114 AN XY: 67284

Gnomad4 AFR AF: 0.00593

Gnomad4 AMR AF: 0.000842

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00187

Gnomad4 SAS AF: 0.000240

Gnomad4 FIN AF: 0.000335

Gnomad4 NFE AF: 0.000127

Gnomad4 OTH AF: 0.00210

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:6

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 06, 2020	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified Uncertain:1 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Jul 21, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 24, 2015	- -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2018

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

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: rs797045268; hg19: chr6-157100116;