6-156778847-GGGCGGCGGCGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGCGGCGGC

Variant names:

• chr6-156778847-G-GGGC
• rs587779747
• NM_001374828.1:c.1191_1193dupCGG

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.1191_1193dupCGG​(p.Gly398dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00216 in 1,403,452 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G398G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0067 (6 hom., cov: 29)
  • Exomes 𝑓: 0.0016 (14 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 4.68
• Publications: 1 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, Orphanet, ClinGen
• Coffin-Siris syndrome 1

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

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 6-156778847-G-GGGC is Benign according to our data. Variant chr6-156778847-G-GGGC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0067 (991/147922) while in subpopulation AFR AF = 0.02 (807/40308). AF 95% confidence interval is 0.0189. There are 6 homozygotes in GnomAd4. There are 484 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 991 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.1191_1193dupCGG	p.Gly398dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.1191_1193dupCGG	p.Gly398dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.1191_1193dupCGG	p.Gly398dup	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.1191_1193dupCGG	p.Gly398dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.1191_1193dupCGG	p.Gly398dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.1191_1193dupCGG	p.Gly398dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.00671 AC: 992 AN: 147818 Hom.: 6 Cov.: 29

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00292

Gnomad EAS AF: 0.00205

Gnomad SAS AF: 0.00322

Gnomad FIN AF: 0.000710

Gnomad MID AF: 0.00333

Gnomad NFE AF: 0.00120

Gnomad OTH AF: 0.00588

GnomAD2 exomes AF: 0.00104 AC: 58 AN: 55508 AF XY: 0.00107

Gnomad AFR exome AF: 0.0179

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.00122

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000563

Gnomad NFE exome AF: 0.000634

Gnomad OTH exome AF: 0.00155

GnomAD4 exome AF: 0.00163 AC: 2043 AN: 1255530 Hom.: 14 Cov.: 37 AF XY: 0.00161 AC XY: 993 AN XY: 617140

African (AFR) AF: 0.0243 AC: 601 AN: 24688

American (AMR) AF: 0.00387 AC: 66 AN: 17064

Ashkenazi Jewish (ASJ) AF: 0.00137 AC: 28 AN: 20424

East Asian (EAS) AF: 0.00199 AC: 55 AN: 27604

South Asian (SAS) AF: 0.00176 AC: 103 AN: 58576

European-Finnish (FIN) AF: 0.000754 AC: 32 AN: 42444

Middle Eastern (MID) AF: 0.00317 AC: 16 AN: 5046

European-Non Finnish (NFE) AF: 0.000967 AC: 976 AN: 1008976

Other (OTH) AF: 0.00327 AC: 166 AN: 50708

GnomAD4 genome AF: 0.00670 AC: 991 AN: 147922 Hom.: 6 Cov.: 29 AF XY: 0.00670 AC XY: 484 AN XY: 72278

African (AFR) AF: 0.0200 AC: 807 AN: 40308

American (AMR) AF: 0.00326 AC: 49 AN: 15016

Ashkenazi Jewish (ASJ) AF: 0.00292 AC: 10 AN: 3420

East Asian (EAS) AF: 0.00206 AC: 10 AN: 4866

South Asian (SAS) AF: 0.00322 AC: 15 AN: 4656

European-Finnish (FIN) AF: 0.000710 AC: 7 AN: 9854

Middle Eastern (MID) AF: 0.00360 AC: 1 AN: 278

European-Non Finnish (NFE) AF: 0.00120 AC: 80 AN: 66586

Other (OTH) AF: 0.00581 AC: 12 AN: 2064

Alfa AF: 0.000632 Hom.: 2

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Coffin-Siris syndrome 1 (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7
Mutation Taster		=78/22	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs587779747; hg19: chr6-157099981; COSMIC: COSV51656229; COSMIC: COSV51656229;