6-156778847-GGGCGGCGGCGGCGGCGGC-GGGCGGCGGCGGCGGC

Position:

• chr6-156778847-GGGCGGCGGCGGCGGCGGC-GGGCGGCGGCGGCGGC

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The NM_001374828.1(ARID1B):​c.1191_1193del​(p.Gly402del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000994 in 1,395,576 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: ARID1B NM_001374828.1 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.68

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 -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778847-GGGC-G is Benign according to our data. Variant chr6-156778847-GGGC-G is described in ClinVar as [Likely_benign]. Clinvar id is 589538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156778847-GGGC-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000419 (62/147912) while in subpopulation AMR AF= 0.00127 (19/15014). AF 95% confidence interval is 0.000829. There are 0 homozygotes in gnomad4. There are 30 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.1191_1193del	p.Gly402del	inframe_deletion	1/20	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.1191_1193del	p.Gly402del	inframe_deletion	1/20	2	NM_001374828.1	ENSP00000490491	A2

Frequencies

GnomAD3 genomes AF: 0.000419 AC: 62 AN: 147808 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000398

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00127

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000429

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000375

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00506 AC: 281 AN: 55508 Hom.: 0 AF XY: 0.00448 AC XY: 147 AN XY: 32826

Gnomad AFR exome AF: 0.0119

Gnomad AMR exome AF: 0.0106

Gnomad ASJ exome AF: 0.00343

Gnomad EAS exome AF: 0.00199

Gnomad SAS exome AF: 0.00538

Gnomad FIN exome AF: 0.00402

Gnomad NFE exome AF: 0.00401

Gnomad OTH exome AF: 0.00620

GnomAD4 exome AF: 0.00106 AC: 1325 AN: 1247664 Hom.: 0 AF XY: 0.00113 AC XY: 695 AN XY: 612864

Gnomad4 AFR exome AF: 0.000979

Gnomad4 AMR exome AF: 0.00416

Gnomad4 ASJ exome AF: 0.00193

Gnomad4 EAS exome AF: 0.000548

Gnomad4 SAS exome AF: 0.00393

Gnomad4 FIN exome AF: 0.00153

Gnomad4 NFE exome AF: 0.000804

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.000419 AC: 62 AN: 147912 Hom.: 0 Cov.: 29 AF XY: 0.000415 AC XY: 30 AN XY: 72274

Gnomad4 AFR AF: 0.000397

Gnomad4 AMR AF: 0.00127

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000430

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000375

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 19, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 10, 2021	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 03, 2018

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. -

ARID1B-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 20, 2019

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). -

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: rs587779747; hg19: chr6-157099981;