rs1554265275

Variant names:

• chr6-156901439-T-TA
• rs1554265275
• NM_001374828.1:c.2051dupA

Your query was ambiguous. Multiple possible variants found:

• chr6-156901439-T-TA
• chr6-156901439-T-TAA

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001374828.1(ARID1B):​c.2051dupA​(p.Tyr684fs) variant causes a frameshift, stop gained change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARID1B NM_001374828.1 frameshift, stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.28
• 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

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-156901439-T-TA is Pathogenic according to our data. Variant chr6-156901439-T-TA is described in ClinVar as Pathogenic. ClinVar VariationId is 438280.Status of the report is no_assertion_criteria_provided, 0 stars.

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.2051dupA	p.Tyr684fs	frameshift stop_gained	Exon 3 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.2051dupA	p.Tyr684fs	frameshift stop_gained	Exon 3 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.2051dupA	p.Tyr684fs	frameshift stop_gained	Exon 3 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.2051dupA	p.Tyr684fs	frameshift stop_gained	Exon 3 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.2090dupA	p.Tyr697fs	frameshift stop_gained	Exon 5 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.2051dupA	p.Tyr684fs	frameshift stop_gained	Exon 3 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Coffin-Siris syndrome 1 Pathogenic:1

Jun 06, 2016

Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3
Mutation Taster		=0/200	disease causing (ClinVar)

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: rs1554265275; hg19: chr6-157222573; COSMIC: COSV99273716;