rs387907142

Variant names:

• chr6-156901502-C-T
• rs387907142
• NM_001374828.1:c.2113C>T

Variant summary

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

The NM_001374828.1(ARID1B):​c.2113C>T​(p.Gln705*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.23
• 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: 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 6-156901502-C-T is Pathogenic according to our data. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-156901502-C-T is described in CliVar as Pathogenic. Clinvar id is 31213.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.2113C>T	p.Gln705*	stop_gained	Exon 3 of 20	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.2113C>T	p.Gln705*	stop_gained	Exon 3 of 20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Coffin-Siris syndrome 1 Pathogenic:1

Mar 18, 2012

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	39
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.99
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		6.2
Vest4		0.80
GERP RS		5.7
PromoterAI		-0.0012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=0/200	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs387907142; hg19: chr6-157222636;