NM_001374828.1:c.1226_1234dupGAGGAGGAG

Variant names:

• chr6-156778889-C-CGGAGGAGGA
• rs747790383
• NM_001374828.1:c.1226_1234dupGAGGAGGAG

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.1226_1234dupGAGGAGGAG​(p.Gly409_Gly411dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000839 in 143,056 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00084 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00079 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.98

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 6-156778889-C-CGGAGGAGGA is Benign according to our data. Variant chr6-156778889-C-CGGAGGAGGA is described in ClinVar as [Likely_benign]. Clinvar id is 589786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000839 (120/143056) while in subpopulation AMR AF= 0.00296 (43/14550). AF 95% confidence interval is 0.00225. There are 0 homozygotes in gnomad4. There are 59 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 120 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.1226_1234dupGAGGAGGAG	p.Gly409_Gly411dup	disruptive_inframe_insertion	Exon 1 of 20	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.1226_1234dupGAGGAGGAG	p.Gly409_Gly411dup	disruptive_inframe_insertion	Exon 1 of 20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes AF: 0.000839 AC: 120 AN: 142982 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00296

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000803

Gnomad OTH AF: 0.00254

GnomAD3 exomes AF: 0.000180 AC: 6 AN: 33354 Hom.: 0 AF XY: 0.000101 AC XY: 2 AN XY: 19836

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00144

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: 0.0000948

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000789 AC: 965 AN: 1223528 Hom.: 1 Cov.: 35 AF XY: 0.000727 AC XY: 436 AN XY: 599372

Gnomad4 AFR exome AF: 0.000125

Gnomad4 AMR exome AF: 0.00268

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000878

Gnomad4 OTH exome AF: 0.00101

GnomAD4 genome AF: 0.000839 AC: 120 AN: 143056 Hom.: 0 Cov.: 29 AF XY: 0.000845 AC XY: 59 AN XY: 69794

Gnomad4 AFR AF: 0.000514

Gnomad4 AMR AF: 0.00296

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000804

Gnomad4 OTH AF: 0.00252

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 25, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ARID1B: BS1 -

Inborn genetic diseases Benign:1

Sep 21, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Oct 24, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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: rs747790383; hg19: chr6-157100023;