chr6-156778268-CCAGCAGCAG-C

Position:

• chr6-156778268-CCAGCAGCAG-C

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.603_611delGCAGCAGCA​(p.Gln202_Gln204del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000292 in 1,536,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.90

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]

ENSG00000271551 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778268-CCAGCAGCAG-C is Benign according to our data. Variant chr6-156778268-CCAGCAGCAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 975342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00041 (62/151370) while in subpopulation AFR AF= 0.000896 (37/41288). AF 95% confidence interval is 0.000668. There are 0 homozygotes in gnomad4. There are 44 alleles in male gnomad4 subpopulation. Median coverage is 30. 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.603_611delGCAGCAGCA	p.Gln202_Gln204del	disruptive_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.603_611delGCAGCAGCA	p.Gln202_Gln204del	disruptive_inframe_deletion	1/20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes AF: 0.000403 AC: 61 AN: 151256 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000874

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000251

Gnomad OTH AF: 0.000962

GnomAD3 exomes AF: 0.000255 AC: 33 AN: 129416 Hom.: 0 AF XY: 0.000187 AC XY: 13 AN XY: 69488

Gnomad AFR exome AF: 0.000464

Gnomad AMR exome AF: 0.000175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000425

Gnomad SAS exome AF: 0.000235

Gnomad FIN exome AF: 0.000410

Gnomad NFE exome AF: 0.000271

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000279 AC: 386 AN: 1385448 Hom.: 0 AF XY: 0.000266 AC XY: 182 AN XY: 683558

Gnomad4 AFR exome AF: 0.00115

Gnomad4 AMR exome AF: 0.000253

Gnomad4 ASJ exome AF: 0.0000798

Gnomad4 EAS exome AF: 0.000169

Gnomad4 SAS exome AF: 0.000165

Gnomad4 FIN exome AF: 0.000193

Gnomad4 NFE exome AF: 0.000272

Gnomad4 OTH exome AF: 0.000347

GnomAD4 genome AF: 0.000410 AC: 62 AN: 151370 Hom.: 0 Cov.: 30 AF XY: 0.000595 AC XY: 44 AN XY: 73994

Gnomad4 AFR AF: 0.000896

Gnomad4 AMR AF: 0.000197

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000251

Gnomad4 OTH AF: 0.000952

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

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	Jul 28, 2020	- -

ARID1B-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 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). -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2021

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. -

Intellectual disability Benign:1

Likely benign, no assertion criteria provided

clinical testing

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

Jan 01, 2019

- -

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: rs587779743; hg19: chr6-157099402;