6-156778292-ACAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant names:

• chr6-156778292-A-ACAGCAGCAGCAGCAGCAG
• rs587779744
• NM_001374828.1:c.618_635dupGCAGCAGCAGCAGCAGCA

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001374828.1(ARID1B):​c.618_635dupGCAGCAGCAGCAGCAGCA​(p.Gln207_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 0.00000329 in 1,518,256 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q212Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 12 publications found

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]

ARID1B Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina, ClinGen
• Coffin-Siris syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000271551 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374828.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	NM_001374828.1	MANE Select	c.618_635dupGCAGCAGCAGCAGCAGCA	p.Gln207_Gln212dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.618_635dupGCAGCAGCAGCAGCAGCA	p.Gln207_Gln212dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.618_635dupGCAGCAGCAGCAGCAGCA	p.Gln207_Gln212dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425412.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.618_635dupGCAGCAGCAGCAGCAGCA	p.Gln207_Gln212dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.618_635dupGCAGCAGCAGCAGCAGCA	p.Gln207_Gln212dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.618_635dupGCAGCAGCAGCAGCAGCA	p.Gln207_Gln212dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.00000688 AC: 1 AN: 145296 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000291 AC: 4 AN: 1372960 Hom.: 0 Cov.: 37 AF XY: 0.00000443 AC XY: 3 AN XY: 677774

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000713 AC: 2 AN: 28048

American (AMR) AF: 0.00 AC: 0 AN: 35068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24812

East Asian (EAS) AF: 0.00 AC: 0 AN: 34778

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5526

European-Non Finnish (NFE) AF: 9.37e-7 AC: 1 AN: 1066902

Other (OTH) AF: 0.00 AC: 0 AN: 56822

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000037155), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000688 AC: 1 AN: 145296 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 71036

African (AFR) AF: 0.0000275 AC: 1 AN: 36338

American (AMR) AF: 0.00 AC: 0 AN: 14968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 4958

South Asian (SAS) AF: 0.00 AC: 0 AN: 4774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67182

Other (OTH) AF: 0.00 AC: 0 AN: 1998

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=77/23	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587779744; hg19: chr6-157099426;