chr6-157207463-C-G

Variant names:

• chr6-157207463-C-G
• rs1554238035
• NM_001374828.1:c.6691C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001374828.1(ARID1B):​c.6691C>G​(p.Gln2231Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.06
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36962107).

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.6691C>G	p.Gln2231Glu	missense	Exon 20 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.6820C>G	p.Gln2274Glu	missense	Exon 21 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.6733C>G	p.Gln2245Glu	missense	Exon 21 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.6691C>G	p.Gln2231Glu	missense	Exon 20 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.6571C>G	p.Gln2191Glu	missense	Exon 21 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.6532C>G	p.Gln2178Glu	missense	Exon 19 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.033	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.1
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.23
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.027	D
Polyphen		0.99	D
Vest4		0.56
MutPred		0.34		Gain of ubiquitination at K2097 (P = 0.0653)
MVP		0.54
MPC		1.5
ClinPred		0.85	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.38
gMVP		0.91
Mutation Taster		=71/29	polymorphism

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: rs1554238035; hg19: chr6-157528597;