6-156777818-CGCGGCGGCGGCG-CGCGGCGGCGGCGGCG

Variant names:

• chr6-156777818-C-CGCG
• rs1046394316
• NM_001374828.1:c.156_158dupGGC

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The NM_001374828.1(ARID1B):​c.156_158dupGGC​(p.Ala53dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,011,732 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 30)
  • Exomes 𝑓: 0.0013 (1 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.490
• 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)

ENSG00000271551 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156777818-C-CGCG is Benign according to our data. Variant chr6-156777818-C-CGCG is described in ClinVar as Likely_benign. ClinVar VariationId is 2579011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00186 (264/142248) while in subpopulation AFR AF = 0.00278 (110/39498). AF 95% confidence interval is 0.00236. There are 1 homozygotes in GnomAd4. There are 125 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 264 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.156_158dupGGC	p.Ala53dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.156_158dupGGC	p.Ala53dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.156_158dupGGC	p.Ala53dup	disruptive_inframe_insertion	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.156_158dupGGC	p.Ala53dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.156_158dupGGC	p.Ala53dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.156_158dupGGC	p.Ala53dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.00185 AC: 263 AN: 142230 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00276

Gnomad AMI AF: 0.00917

Gnomad AMR AF: 0.00110

Gnomad ASJ AF: 0.000298

Gnomad EAS AF: 0.00166

Gnomad SAS AF: 0.00258

Gnomad FIN AF: 0.000375

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.00154

GnomAD4 exome AF: 0.00131 AC: 1140 AN: 869484 Hom.: 1 Cov.: 18 AF XY: 0.00129 AC XY: 522 AN XY: 404808

African (AFR) AF: 0.00177 AC: 30 AN: 16958

American (AMR) AF: 0.000869 AC: 2 AN: 2302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6598

East Asian (EAS) AF: 0.00100 AC: 7 AN: 6968

South Asian (SAS) AF: 0.00285 AC: 50 AN: 17514

European-Finnish (FIN) AF: 0.000216 AC: 1 AN: 4626

Middle Eastern (MID) AF: 0.000541 AC: 1 AN: 1850

European-Non Finnish (NFE) AF: 0.00130 AC: 1015 AN: 782810

Other (OTH) AF: 0.00114 AC: 34 AN: 29858

GnomAD4 genome AF: 0.00186 AC: 264 AN: 142248 Hom.: 1 Cov.: 30 AF XY: 0.00181 AC XY: 125 AN XY: 69172

African (AFR) AF: 0.00278 AC: 110 AN: 39498

American (AMR) AF: 0.00110 AC: 16 AN: 14534

Ashkenazi Jewish (ASJ) AF: 0.000298 AC: 1 AN: 3358

East Asian (EAS) AF: 0.00166 AC: 8 AN: 4812

South Asian (SAS) AF: 0.00259 AC: 12 AN: 4630

European-Finnish (FIN) AF: 0.000375 AC: 3 AN: 8006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.00160 AC: 103 AN: 64296

Other (OTH) AF: 0.00152 AC: 3 AN: 1972

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49

Splicing

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

Other links and lift over

dbSNP: rs1046394316; hg19: chr6-157098952;