NM_001374828.1:c.266G>C

Variant names:

• chr6-156777946-G-C
• rs1057518648
• NM_001374828.1:c.266G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_001374828.1(ARID1B):​c.266G>C​(p.Gly89Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G89D) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.550

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]

ENSG00000271551 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr6-156777946-G-A is described in Lovd as [Likely_pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.20149317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.266G>C	p.Gly89Ala	missense_variant	Exon 1 of 20	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.266G>C	p.Gly89Ala	missense_variant	Exon 1 of 20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.55
DEOGEN2	Benign	0.012	.;T;.;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.44	T;T;T;T
M_CAP	Pathogenic	0.75	D
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.0	.;N;N;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.090	.;N;.;.
REVEL	Benign	0.036
Sift	Pathogenic	0.0	.;D;.;.
Sift4G	Benign	0.81	.;T;.;.
Vest4		0.071
MutPred		0.39		.;Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);
MVP		0.13
MPC		0.31
ClinPred		0.32	T
GERP RS		2.6
Varity_R		0.19
gMVP		0.34

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: rs1057518648; hg19: chr6-157099080; COSMIC: COSV51657308; COSMIC: COSV51657308;