rs1274057762

chr6-157201068-G-Achr6-157201068-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001374828.1(ARID1B):c.4843G>A(p.Gly1615Ser) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1615V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.39

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19751924).
• BP6: Variant 6-157201068-G-A is Benign according to our data. Variant chr6-157201068-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 434388.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.4843G>A	p.Gly1615Ser	missense_variant	18/20	ENST00000636930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.4843G>A	p.Gly1615Ser	missense_variant	18/20	2	NM_001374828.1	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 16, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	23
Dann	Benign	0.97
Eigen	Benign	-0.13
Eigen_PC	Benign	0.092
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.72	T
MutationTaster	Benign	0.96	D;D;D;D
PrimateAI	Uncertain	0.51	T
REVEL	Benign	0.12
Polyphen		0.045, 0.075	.;B;.;B;.;.;.;.;.
Vest4		0.46
MutPred		0.13		.;Gain of phosphorylation at G1479 (P = 0.0364);.;.;.;.;.;.;.;
MVP		0.38
MPC		1.1
ClinPred		0.85	D
GERP RS		5.1
Varity_R		0.21
gMVP		0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs1274057762; hg19: chr6-157522202;