6-156778982-AGGCGGCGGC-AGGC

Variant names:

• chr6-156778982-AGGCGGC-A
• rs797045268
• NM_001374828.1:c.1315_1320delGGCGGC

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.1315_1320delGGCGGC​(p.Gly439_Gly440del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,262,726 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: ARID1B NM_001374828.1 conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.82
• 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, 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 6-156778982-AGGCGGC-A is Benign according to our data. Variant chr6-156778982-AGGCGGC-A is described in ClinVar as Likely_benign. ClinVar VariationId is 434356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0002 (225/1125428) while in subpopulation AMR AF = 0.000714 (6/8406). AF 95% confidence interval is 0.000311. There are 1 homozygotes in GnomAdExome4. There are 111 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
• BS2: High AC in GnomAd4 at 21 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.1315_1320delGGCGGC	p.Gly439_Gly440del	conservative_inframe_deletion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.1315_1320delGGCGGC	p.Gly439_Gly440del	conservative_inframe_deletion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.1315_1320delGGCGGC	p.Gly439_Gly440del	conservative_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.1315_1320delGGCGGC	p.Gly439_Gly440del	conservative_inframe_deletion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.1315_1320delGGCGGC	p.Gly439_Gly440del	conservative_inframe_deletion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.1315_1320delGGCGGC	p.Gly439_Gly440del	conservative_inframe_deletion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.000153 AC: 21 AN: 137298 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000140

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000701

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000111

Gnomad OTH AF: 0.00160

GnomAD2 exomes AF: 0.00 AC: 0 AN: 1892 AF XY: 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000200 AC: 225 AN: 1125428 Hom.: 1 AF XY: 0.000205 AC XY: 111 AN XY: 541866

African (AFR) AF: 0.00 AC: 0 AN: 22846

American (AMR) AF: 0.000714 AC: 6 AN: 8406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14450

East Asian (EAS) AF: 0.000227 AC: 6 AN: 26406

South Asian (SAS) AF: 0.0000375 AC: 1 AN: 26682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3096

European-Non Finnish (NFE) AF: 0.000185 AC: 176 AN: 953508

Other (OTH) AF: 0.000794 AC: 36 AN: 45328

GnomAD4 genome AF: 0.000153 AC: 21 AN: 137298 Hom.: 0 Cov.: 29 AF XY: 0.000134 AC XY: 9 AN XY: 67178

African (AFR) AF: 0.000164 AC: 6 AN: 36654

American (AMR) AF: 0.000140 AC: 2 AN: 14246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3284

East Asian (EAS) AF: 0.000701 AC: 3 AN: 4280

South Asian (SAS) AF: 0.00 AC: 0 AN: 4174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.000111 AC: 7 AN: 62790

Other (OTH) AF: 0.00160 AC: 3 AN: 1878

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8
Mutation Taster		=175/25	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs797045268; hg19: chr6-157100116;