6-156778889-CGGAGGAGGAGGAGGA-CGGA

Variant names:

• chr6-156778889-CGGAGGAGGAGGA-C
• rs747790383
• NM_001374828.1:c.1223_1234delGAGGAGGAGGAG

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The NM_001374828.1(ARID1B):​c.1223_1234delGAGGAGGAGGAG​(p.Gly408_Gly411del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000776 in 1,366,606 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 DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:5
• Conservation: PhyloP100: 3.18
• Publications: 0 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: Illumina, ClinGen, Orphanet
• Coffin-Siris syndrome 1

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

ENSG00000296922 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778889-CGGAGGAGGAGGA-C is Benign according to our data. Variant chr6-156778889-CGGAGGAGGAGGA-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 591999.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 = 0.000168 (24/143056) while in subpopulation EAS AF = 0.00298 (14/4694). AF 95% confidence interval is 0.0018. There are 0 homozygotes in GnomAd4. There are 10 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 24 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	NM_001374828.1	MANE Select	c.1223_1234delGAGGAGGAGGAG	p.Gly408_Gly411del	disruptive_inframe_deletion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.1223_1234delGAGGAGGAGGAG	p.Gly408_Gly411del	disruptive_inframe_deletion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.1223_1234delGAGGAGGAGGAG	p.Gly408_Gly411del	disruptive_inframe_deletion	Exon 1 of 21	NP_001425412.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.1223_1234delGAGGAGGAGGAG	p.Gly408_Gly411del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.1223_1234delGAGGAGGAGGAG	p.Gly408_Gly411del	disruptive_inframe_deletion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.1223_1234delGAGGAGGAGGAG	p.Gly408_Gly411del	disruptive_inframe_deletion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.000161 AC: 23 AN: 142982 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00297

Gnomad SAS AF: 0.000224

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000618

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000670 AC: 82 AN: 1223550 Hom.: 0 AF XY: 0.0000634 AC XY: 38 AN XY: 599380

African (AFR) AF: 0.000292 AC: 7 AN: 23958

American (AMR) AF: 0.0000687 AC: 1 AN: 14566

Ashkenazi Jewish (ASJ) AF: 0.0000537 AC: 1 AN: 18616

East Asian (EAS) AF: 0.000924 AC: 25 AN: 27060

South Asian (SAS) AF: 0.000114 AC: 6 AN: 52790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4406

European-Non Finnish (NFE) AF: 0.0000373 AC: 37 AN: 992596

Other (OTH) AF: 0.000101 AC: 5 AN: 49424

GnomAD4 genome AF: 0.000168 AC: 24 AN: 143056 Hom.: 0 Cov.: 29 AF XY: 0.000143 AC XY: 10 AN XY: 69794

African (AFR) AF: 0.000128 AC: 5 AN: 38934

American (AMR) AF: 0.00 AC: 0 AN: 14550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3376

East Asian (EAS) AF: 0.00298 AC: 14 AN: 4694

South Asian (SAS) AF: 0.000225 AC: 1 AN: 4448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 254

European-Non Finnish (NFE) AF: 0.0000618 AC: 4 AN: 64716

Other (OTH) AF: 0.00 AC: 0 AN: 1982

Alfa AF: 0.0000862 Hom.: 1

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	3	not provided (4)
-	-	1	ARID1B-related disorder (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
Mutation Taster		=194/6	polymorphism

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs747790383; hg19: chr6-157100023;