6-156778982-AGGCGGCGGC-A

Variant names:

• chr6-156778982-AGGCGGCGGC-A
• rs797045268
• NM_001374828.1:c.1312_1320delGGCGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The ENST00000636930.2(ARID1B):​c.1312_1320delGGCGGCGGC​(p.Gly438_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 0.0000341 in 1,262,838 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G438G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000036 (1 hom.)
• Consequence: ARID1B ENST00000636930.2 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: 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: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000636930.2
• BS2: High AC in GnomAdExome4 at 41 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636930.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	NM_001374828.1	MANE Select	c.1312_1320delGGCGGCGGC	p.Gly438_Gly440del	conservative_inframe_deletion	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.1312_1320delGGCGGCGGC	p.Gly438_Gly440del	conservative_inframe_deletion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.1312_1320delGGCGGCGGC	p.Gly438_Gly440del	conservative_inframe_deletion	Exon 1 of 21	NP_001425412.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.1312_1320delGGCGGCGGC	p.Gly438_Gly440del	conservative_inframe_deletion	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.1312_1320delGGCGGCGGC	p.Gly438_Gly440del	conservative_inframe_deletion	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.1312_1320delGGCGGCGGC	p.Gly438_Gly440del	conservative_inframe_deletion	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.0000146 AC: 2 AN: 137298 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000319

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000364 AC: 41 AN: 1125434 Hom.: 1 AF XY: 0.0000461 AC XY: 25 AN XY: 541872

African (AFR) AF: 0.0000438 AC: 1 AN: 22846

American (AMR) AF: 0.00 AC: 0 AN: 8406

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 26406

South Asian (SAS) AF: 0.00 AC: 0 AN: 26688

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: 0.0000399 AC: 38 AN: 953508

Other (OTH) AF: 0.0000441 AC: 2 AN: 45328

GnomAD4 genome AF: 0.0000146 AC: 2 AN: 137404 Hom.: 0 Cov.: 29 AF XY: 0.0000297 AC XY: 2 AN XY: 67288

African (AFR) AF: 0.00 AC: 0 AN: 36756

American (AMR) AF: 0.00 AC: 0 AN: 14254

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4272

South Asian (SAS) AF: 0.00 AC: 0 AN: 4168

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 202

European-Non Finnish (NFE) AF: 0.0000319 AC: 2 AN: 62786

Other (OTH) AF: 0.00 AC: 0 AN: 1904

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8
Mutation Taster		=181/19	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;