6-156778889-CGGAGGAGGAGGAGGA-CGGAGGAGGAGGAGGAGGA

Variant names:

• chr6-156778889-C-CGGA
• rs747790383
• NM_001374828.1:c.1232_1234dupGAG

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.1232_1234dupGAG​(p.Gly411dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,366,378 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0017 (1 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.98
• 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-C-CGGA is Benign according to our data. Variant chr6-156778889-C-CGGA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00217 (311/143042) while in subpopulation SAS AF = 0.00427 (19/4448). AF 95% confidence interval is 0.0028. There are 0 homozygotes in GnomAd4. There are 141 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 311 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.1232_1234dupGAG	p.Gly411dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.1232_1234dupGAG	p.Gly411dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.1232_1234dupGAG	p.Gly411dup	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.1232_1234dupGAG	p.Gly411dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.1232_1234dupGAG	p.Gly411dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.1232_1234dupGAG	p.Gly411dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.00216 AC: 309 AN: 142968 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00227

Gnomad ASJ AF: 0.00118

Gnomad EAS AF: 0.00106

Gnomad SAS AF: 0.00403

Gnomad FIN AF: 0.000648

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00198

Gnomad OTH AF: 0.00102

GnomAD2 exomes AF: 0.000600 AC: 20 AN: 33354 AF XY: 0.000605

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000864

Gnomad ASJ exome AF: 0.000421

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000113

Gnomad NFE exome AF: 0.000853

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00171 AC: 2097 AN: 1223336 Hom.: 1 Cov.: 35 AF XY: 0.00172 AC XY: 1028 AN XY: 599276

African (AFR) AF: 0.00292 AC: 70 AN: 23946

American (AMR) AF: 0.00117 AC: 17 AN: 14564

Ashkenazi Jewish (ASJ) AF: 0.00183 AC: 34 AN: 18612

East Asian (EAS) AF: 0.00222 AC: 60 AN: 27060

South Asian (SAS) AF: 0.00313 AC: 165 AN: 52762

European-Finnish (FIN) AF: 0.000523 AC: 21 AN: 40126

Middle Eastern (MID) AF: 0.00295 AC: 13 AN: 4406

European-Non Finnish (NFE) AF: 0.00163 AC: 1613 AN: 992446

Other (OTH) AF: 0.00210 AC: 104 AN: 49414

GnomAD4 genome AF: 0.00217 AC: 311 AN: 143042 Hom.: 0 Cov.: 29 AF XY: 0.00202 AC XY: 141 AN XY: 69784

African (AFR) AF: 0.00290 AC: 113 AN: 38928

American (AMR) AF: 0.00234 AC: 34 AN: 14548

Ashkenazi Jewish (ASJ) AF: 0.00118 AC: 4 AN: 3376

East Asian (EAS) AF: 0.00107 AC: 5 AN: 4694

South Asian (SAS) AF: 0.00427 AC: 19 AN: 4448

European-Finnish (FIN) AF: 0.000648 AC: 6 AN: 9254

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

European-Non Finnish (NFE) AF: 0.00198 AC: 128 AN: 64714

Other (OTH) AF: 0.00101 AC: 2 AN: 1982

Alfa AF: 0.000690 Hom.: 1

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not provided (6)
-	-	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		2.0
Mutation Taster		=69/31	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs747790383; hg19: chr6-157100023; COSMIC: COSV104368487;