rs1057520140

Positions:

• chr6-156778030-T-A
• chr6-156778030-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001374828.1(ARID1B):​c.350T>A​(p.Leu117Gln) 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. L117P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20743042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.350T>A	p.Leu117Gln	missense_variant	1/20	ENST00000636930.2
LOC115308161	NR_163974.1	n.273+216A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.350T>A	p.Leu117Gln	missense_variant	1/20	2	NM_001374828.1	A2
	ENST00000603191.2	n.177+216A>T		intron_variant, non_coding_transcript_variant		3

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	0.11
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.012	.;T;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.43	T;T;T;T
M_CAP	Pathogenic	0.92	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;N;N;N
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.12	.;N;.;.
REVEL	Benign	0.034
Sift	Pathogenic	0.0	.;D;.;.
Sift4G	Uncertain	0.029	.;D;.;.
Vest4		0.22
MutPred		0.25		.;Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);
MVP		0.26
MPC		0.31
ClinPred		0.35	T
GERP RS		0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.26
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-157099164;