chr6-156778847-G-GGGCGGC

Variant names:

• chr6-156778847-G-GGGCGGC
• rs587779747
• NM_001374828.1:c.1188_1193dupCGGCGG

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.1188_1193dupCGGCGG​(p.Gly397_Gly398dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0004 in 1,403,494 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00060 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• 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-GGGCGGC is Benign according to our data. Variant chr6-156778847-G-GGGCGGC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000602 (89/147924) while in subpopulation AMR AF = 0.00107 (16/15016). AF 95% confidence interval is 0.000668. There are 0 homozygotes in GnomAd4. There are 40 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 89 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.1188_1193dupCGGCGG	p.Gly397_Gly398dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.1188_1193dupCGGCGG	p.Gly397_Gly398dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.1188_1193dupCGGCGG	p.Gly397_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.1188_1193dupCGGCGG	p.Gly397_Gly398dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.1188_1193dupCGGCGG	p.Gly397_Gly398dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.1188_1193dupCGGCGG	p.Gly397_Gly398dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.000602 AC: 89 AN: 147820 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000373

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00107

Gnomad ASJ AF: 0.00585

Gnomad EAS AF: 0.000205

Gnomad SAS AF: 0.000429

Gnomad FIN AF: 0.000102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000481

Gnomad OTH AF: 0.000979

GnomAD2 exomes AF: 0.000234 AC: 13 AN: 55508 AF XY: 0.000244

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000171

Gnomad ASJ exome AF: 0.00122

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000241

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000377 AC: 473 AN: 1255570 Hom.: 0 Cov.: 37 AF XY: 0.000410 AC XY: 253 AN XY: 617172

African (AFR) AF: 0.000283 AC: 7 AN: 24704

American (AMR) AF: 0.000410 AC: 7 AN: 17064

Ashkenazi Jewish (ASJ) AF: 0.00568 AC: 116 AN: 20424

East Asian (EAS) AF: 0.000181 AC: 5 AN: 27604

South Asian (SAS) AF: 0.000597 AC: 35 AN: 58582

European-Finnish (FIN) AF: 0.0000707 AC: 3 AN: 42442

Middle Eastern (MID) AF: 0.00139 AC: 7 AN: 5046

European-Non Finnish (NFE) AF: 0.000250 AC: 252 AN: 1008992

Other (OTH) AF: 0.000808 AC: 41 AN: 50712

GnomAD4 genome AF: 0.000602 AC: 89 AN: 147924 Hom.: 0 Cov.: 29 AF XY: 0.000553 AC XY: 40 AN XY: 72280

African (AFR) AF: 0.000372 AC: 15 AN: 40312

American (AMR) AF: 0.00107 AC: 16 AN: 15016

Ashkenazi Jewish (ASJ) AF: 0.00585 AC: 20 AN: 3420

East Asian (EAS) AF: 0.000206 AC: 1 AN: 4866

South Asian (SAS) AF: 0.000430 AC: 2 AN: 4656

European-Finnish (FIN) AF: 0.000102 AC: 1 AN: 9852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.000481 AC: 32 AN: 66586

Other (OTH) AF: 0.000969 AC: 2 AN: 2064

Alfa AF: 0.000237 Hom.: 2

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	1	ARID1B-related disorder (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: COSV105108639;