6-156935471-G-C

Variant names:

• chr6-156935471-G-C
• rs142897795
• NM_001374828.1:c.2142G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001374828.1(ARID1B):​c.2142G>C​(p.Met714Ile) 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. 13/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M714T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.32
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13115162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.2142G>C	p.Met714Ile	missense_variant	Exon 4 of 20	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.2142G>C	p.Met714Ile	missense_variant	Exon 4 of 20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	.;T;.;.;.;T;T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	T;T;T;T;D;T;D;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.13	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;N;N;.;.;.;.;.
PhyloP100		3.3
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.66	.;N;.;.;.;N;.;.
REVEL	Benign	0.079
Sift	Uncertain	0.024	.;D;.;.;.;D;.;.
Sift4G	Benign	0.49	.;T;.;.;.;T;.;.
Polyphen		0.15, 0.23	.;B;.;B;.;.;.;.
Vest4		0.54
MutPred		0.15		.;Gain of glycosylation at S632 (P = 0.0638);Gain of glycosylation at S632 (P = 0.0638);.;.;.;.;.;
MVP		0.32
MPC		0.38
ClinPred		0.52	D
GERP RS		4.8
PromoterAI		-0.00060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.13
Mutation Taster		=94/6	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: rs142897795; hg19: chr6-157256605;