6-156778871-CGGA-CGGAGGA

Position:

• chr6-156778871-CGGA-CGGAGGA

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.1203_1205dupAGG​(p.Gly402dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000948 in 1,340,152 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000075 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000097 (1 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.22

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 6-156778871-C-CGGA is Benign according to our data. Variant chr6-156778871-C-CGGA is described in ClinVar as [Likely_benign]. Clinvar id is 589228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000749 (11/146924) while in subpopulation EAS AF= 0.00125 (6/4804). AF 95% confidence interval is 0.000543. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.1203_1205dupAGG	p.Gly402dup	disruptive_inframe_insertion	1/20	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.1203_1205dupAGG	p.Gly402dup	disruptive_inframe_insertion	1/20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes AF: 0.0000749 AC: 11 AN: 146830 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00124

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000453

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000277 AC: 12 AN: 43244 Hom.: 0 AF XY: 0.000314 AC XY: 8 AN XY: 25448

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000386

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00518

Gnomad SAS exome AF: 0.000550

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000972 AC: 116 AN: 1193228 Hom.: 1 Cov.: 37 AF XY: 0.000106 AC XY: 62 AN XY: 583628

Gnomad4 AFR exome AF: 0.0000850

Gnomad4 AMR exome AF: 0.000203

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000375

Gnomad4 SAS exome AF: 0.000227

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000824

Gnomad4 OTH exome AF: 0.000209

GnomAD4 genome AF: 0.0000749 AC: 11 AN: 146924 Hom.: 0 Cov.: 30 AF XY: 0.0000836 AC XY: 6 AN XY: 71754

Gnomad4 AFR AF: 0.0000249

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00125

Gnomad4 SAS AF: 0.000215

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000453

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	Jan 28, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 26, 2021	- -

ARID1B-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 27, 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

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 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. -

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: rs587779748; hg19: chr6-157100005;