6-156778970-G-GGCAGCA

Variant names:

• chr6-156778970-G-GGCAGCA
• rs797045267
• NM_001374828.1:c.1295_1300dupCAGCAG

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP3 BP6 BS2_Supporting

The NM_001374828.1(ARID1B):​c.1295_1300dupCAGCAG​(p.Ala432_Ala433dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 1,280,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G434G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000048 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 2.52
• 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: Likely_benign. The variant received -3 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778970-G-GGCAGCA is Benign according to our data. Variant chr6-156778970-G-GGCAGCA is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 588748.
• BS2: High AC in GnomAd4 at 7 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.1295_1300dupCAGCAG	p.Ala432_Ala433dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.1295_1300dupCAGCAG	p.Ala432_Ala433dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.1295_1300dupCAGCAG	p.Ala432_Ala433dup	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.1295_1300dupCAGCAG	p.Ala432_Ala433dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.1295_1300dupCAGCAG	p.Ala432_Ala433dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.1295_1300dupCAGCAG	p.Ala432_Ala433dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.0000477 AC: 7 AN: 146666 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000753

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000216

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000454

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000159 AC: 18 AN: 1134222 Hom.: 0 Cov.: 35 AF XY: 0.0000220 AC XY: 12 AN XY: 546384

African (AFR) AF: 0.00 AC: 0 AN: 23042

American (AMR) AF: 0.00 AC: 0 AN: 8630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14728

East Asian (EAS) AF: 0.0000373 AC: 1 AN: 26806

South Asian (SAS) AF: 0.00 AC: 0 AN: 27668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3168

European-Non Finnish (NFE) AF: 0.0000157 AC: 15 AN: 958304

Other (OTH) AF: 0.0000436 AC: 2 AN: 45870

GnomAD4 genome AF: 0.0000477 AC: 7 AN: 146770 Hom.: 0 Cov.: 29 AF XY: 0.0000557 AC XY: 4 AN XY: 71778

African (AFR) AF: 0.0000751 AC: 3 AN: 39966

American (AMR) AF: 0.00 AC: 0 AN: 14946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3426

East Asian (EAS) AF: 0.00 AC: 0 AN: 4762

South Asian (SAS) AF: 0.000216 AC: 1 AN: 4630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9770

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.0000454 AC: 3 AN: 66102

Other (OTH) AF: 0.00 AC: 0 AN: 2020

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=78/22	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs797045267; hg19: chr6-157100104;