6-156778292-A-ACAGCAG

Variant names:

• chr6-156778292-A-ACAGCAG
• rs587779744
• NM_001374828.1:c.630_635dupGCAGCA

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.630_635dupGCAGCA​(p.Gln211_Gln212dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00713 in 145,394 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0071 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0079 (27 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:6
• Conservation: PhyloP100: 2.46

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 6-156778292-A-ACAGCAG is Benign according to our data. Variant chr6-156778292-A-ACAGCAG is described in ClinVar as [Likely_benign]. Clinvar id is 126329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00713 (1037/145394) while in subpopulation NFE AF= 0.00927 (623/67172). AF 95% confidence interval is 0.00867. There are 5 homozygotes in gnomad4. There are 454 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1037 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.630_635dupGCAGCA	p.Gln211_Gln212dup	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.630_635dupGCAGCA	p.Gln211_Gln212dup	disruptive_inframe_insertion	Exon 1 of 20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes AF: 0.00714 AC: 1038 AN: 145294 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00614

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.00468

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.000403

Gnomad SAS AF: 0.00168

Gnomad FIN AF: 0.00727

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00929

Gnomad OTH AF: 0.00651

GnomAD3 exomes AF: 0.00494 AC: 624 AN: 126374 Hom.: 0 AF XY: 0.00479 AC XY: 325 AN XY: 67906

Gnomad AFR exome AF: 0.00368

Gnomad AMR exome AF: 0.00524

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000212

Gnomad SAS exome AF: 0.000912

Gnomad FIN exome AF: 0.00425

Gnomad NFE exome AF: 0.00859

Gnomad OTH exome AF: 0.00585

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00789 AC: 10833 AN: 1372320 Hom.: 27 Cov.: 37 AF XY: 0.00757 AC XY: 5128 AN XY: 677498

Gnomad4 AFR exome AF: 0.00503

Gnomad4 AMR exome AF: 0.00528

Gnomad4 ASJ exome AF: 0.0000806

Gnomad4 EAS exome AF: 0.000144

Gnomad4 SAS exome AF: 0.000968

Gnomad4 FIN exome AF: 0.00508

Gnomad4 NFE exome AF: 0.00922

Gnomad4 OTH exome AF: 0.00637

GnomAD4 genome AF: 0.00713 AC: 1037 AN: 145394 Hom.: 5 Cov.: 31 AF XY: 0.00638 AC XY: 454 AN XY: 71142

Gnomad4 AFR AF: 0.00612

Gnomad4 AMR AF: 0.00467

Gnomad4 ASJ AF: 0.000293

Gnomad4 EAS AF: 0.000405

Gnomad4 SAS AF: 0.00168

Gnomad4 FIN AF: 0.00727

Gnomad4 NFE AF: 0.00927

Gnomad4 OTH AF: 0.00644

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Dec 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ARID1B: BS1 -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 19, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jul 17, 2014

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Aug 30, 2022

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

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: rs587779744; hg19: chr6-157099426;