6-156778889-CGGAGGAGGAGGAGGA-CGGAGGAGGAGGAGGAGGAGGA

Variant names:

• chr6-156778889-C-CGGAGGA
• rs747790383
• NM_001374828.1:c.1229_1234dupGAGGAG

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.1229_1234dupGAGGAG​(p.Gly410_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 0.000454 in 1,366,588 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00047 (0 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• 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: Orphanet, Illumina, 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 6-156778889-C-CGGAGGA is Benign according to our data. Variant chr6-156778889-C-CGGAGGA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 588854.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 = 0.00035 (50/143054) while in subpopulation SAS AF = 0.000674 (3/4448). AF 95% confidence interval is 0.000334. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 50 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.1229_1234dupGAGGAG	p.Gly410_Gly411dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.1229_1234dupGAGGAG	p.Gly410_Gly411dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.1229_1234dupGAGGAG	p.Gly410_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.1229_1234dupGAGGAG	p.Gly410_Gly411dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.1229_1234dupGAGGAG	p.Gly410_Gly411dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.1229_1234dupGAGGAG	p.Gly410_Gly411dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.000350 AC: 50 AN: 142980 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000412

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000688

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000672

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000464

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000180 AC: 6 AN: 33354 AF XY: 0.000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000948

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000466 AC: 570 AN: 1223534 Hom.: 0 Cov.: 35 AF XY: 0.000479 AC XY: 287 AN XY: 599374

African (AFR) AF: 0.000209 AC: 5 AN: 23956

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18616

East Asian (EAS) AF: 0.000222 AC: 6 AN: 27064

South Asian (SAS) AF: 0.000606 AC: 32 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: 0.000493 AC: 489 AN: 992578

Other (OTH) AF: 0.000749 AC: 37 AN: 49424

GnomAD4 genome AF: 0.000350 AC: 50 AN: 143054 Hom.: 0 Cov.: 29 AF XY: 0.000272 AC XY: 19 AN XY: 69794

African (AFR) AF: 0.000411 AC: 16 AN: 38934

American (AMR) AF: 0.0000687 AC: 1 AN: 14550

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4694

South Asian (SAS) AF: 0.000674 AC: 3 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: 0.000464 AC: 30 AN: 64714

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

Alfa AF: 0.00 Hom.: 1

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

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;