6-156778871-CGGAGGAGGA-CGGAGGA

Variant names:

• chr6-156778871-CGGA-C
• rs587779748
• NM_001374828.1:c.1203_1205delAGG

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.1203_1205delAGG​(p.Gly402del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,339,750 control chromosomes in the GnomAD database, including 89 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G401G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0092 (11 hom., cov: 29)
  • Exomes 𝑓: 0.012 (78 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 2.06
• Publications: 2 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 6-156778871-CGGA-C is Benign according to our data. Variant chr6-156778871-CGGA-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 126340.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 = 0.0092 (1351/146914) while in subpopulation SAS AF = 0.0151 (70/4650). AF 95% confidence interval is 0.0122. There are 11 homozygotes in GnomAd4. There are 654 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1351 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.1203_1205delAGG	p.Gly402del	disruptive_inframe_deletion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.1203_1205delAGG	p.Gly402del	disruptive_inframe_deletion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.1203_1205delAGG	p.Gly402del	disruptive_inframe_deletion	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.1203_1205delAGG	p.Gly402del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.1203_1205delAGG	p.Gly402del	disruptive_inframe_deletion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.1203_1205delAGG	p.Gly402del	disruptive_inframe_deletion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.00921 AC: 1352 AN: 146820 Hom.: 11 Cov.: 29

Gnomad AFR AF: 0.00180

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0430

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0150

Gnomad FIN AF: 0.00506

Gnomad MID AF: 0.0142

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.00846

GnomAD2 exomes AF: 0.0119 AC: 513 AN: 43244 AF XY: 0.0130

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00946

Gnomad ASJ exome AF: 0.0409

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00487

Gnomad NFE exome AF: 0.0111

Gnomad OTH exome AF: 0.0108

GnomAD4 exome AF: 0.0116 AC: 13853 AN: 1192836 Hom.: 78 AF XY: 0.0119 AC XY: 6930 AN XY: 583416

African (AFR) AF: 0.00149 AC: 35 AN: 23530

American (AMR) AF: 0.00860 AC: 127 AN: 14764

Ashkenazi Jewish (ASJ) AF: 0.0432 AC: 787 AN: 18202

East Asian (EAS) AF: 0.0000375 AC: 1 AN: 26690

South Asian (SAS) AF: 0.0136 AC: 656 AN: 48338

European-Finnish (FIN) AF: 0.00610 AC: 237 AN: 38854

Middle Eastern (MID) AF: 0.0103 AC: 47 AN: 4560

European-Non Finnish (NFE) AF: 0.0117 AC: 11337 AN: 970076

Other (OTH) AF: 0.0131 AC: 626 AN: 47822

GnomAD4 genome AF: 0.00920 AC: 1351 AN: 146914 Hom.: 11 Cov.: 29 AF XY: 0.00912 AC XY: 654 AN XY: 71748

African (AFR) AF: 0.00180 AC: 72 AN: 40090

American (AMR) AF: 0.0105 AC: 156 AN: 14888

Ashkenazi Jewish (ASJ) AF: 0.0430 AC: 146 AN: 3398

East Asian (EAS) AF: 0.00 AC: 0 AN: 4804

South Asian (SAS) AF: 0.0151 AC: 70 AN: 4650

European-Finnish (FIN) AF: 0.00506 AC: 49 AN: 9692

Middle Eastern (MID) AF: 0.0114 AC: 3 AN: 264

European-Non Finnish (NFE) AF: 0.0116 AC: 769 AN: 66228

Other (OTH) AF: 0.00839 AC: 17 AN: 2026

Alfa AF: 0.00861 Hom.: 8

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs587779748; hg19: chr6-157100005; COSMIC: COSV51656887; COSMIC: COSV51656887;