6-156778283-GCAGCAGCAA-GCAGCAGCAACAGCAGCAA

Variant names:

• chr6-156778283-G-GCAGCAGCAA
• rs797045274
• NM_001374828.1:c.612_620dupACAGCAGCA

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The NM_001374828.1(ARID1B):​c.612_620dupACAGCAGCA​(p.Gln205_Gln207dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000132 in 151,524 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q207Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000037 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 3.85
• 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

ENSG00000271551 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_001374828.1

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	NM_001374828.1	MANE Select	c.612_620dupACAGCAGCA	p.Gln205_Gln207dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.612_620dupACAGCAGCA	p.Gln205_Gln207dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.612_620dupACAGCAGCA	p.Gln205_Gln207dup	disruptive_inframe_insertion	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.612_620dupACAGCAGCA	p.Gln205_Gln207dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.612_620dupACAGCAGCA	p.Gln205_Gln207dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.612_620dupACAGCAGCA	p.Gln205_Gln207dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151524 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000213 AC: 3 AN: 140824 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000816

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000193

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000374 AC: 52 AN: 1389364 Hom.: 0 Cov.: 37 AF XY: 0.0000350 AC XY: 24 AN XY: 685404

African (AFR) AF: 0.00 AC: 0 AN: 31442

American (AMR) AF: 0.0000562 AC: 2 AN: 35618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25102

East Asian (EAS) AF: 0.00 AC: 0 AN: 35634

South Asian (SAS) AF: 0.00 AC: 0 AN: 79042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42632

Middle Eastern (MID) AF: 0.000355 AC: 2 AN: 5628

European-Non Finnish (NFE) AF: 0.0000427 AC: 46 AN: 1076498

Other (OTH) AF: 0.0000346 AC: 2 AN: 57768

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151524 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74000

African (AFR) AF: 0.0000242 AC: 1 AN: 41242

American (AMR) AF: 0.00 AC: 0 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67788

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9
Mutation Taster		=74/26	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs797045274; hg19: chr6-157099417; COSMIC: COSV99034271;