rs776745618

Positions:

• chr6-156778126-A-C
• chr6-156778126-A-G
• chr6-156778126-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001374828.1(ARID1B):​c.446A>C​(p.Asn149Thr) 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. 12/21 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. N149S) 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: 1.24

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28096056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.446A>C	p.Asn149Thr	missense_variant	1/20	ENST00000636930.2	NP_001361757.1
LOC115308161	NR_163974.1	n.273+120T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.446A>C	p.Asn149Thr	missense_variant	1/20	2	NM_001374828.1	ENSP00000490491	A2
	ENST00000603191.2	n.177+120T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Benign	0.89
DEOGEN2	Benign	0.019	.;T;.;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.40	T;T;T;T
M_CAP	Pathogenic	0.75	D
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;N;N;N
MutationTaster	Benign	0.88	N;N;N;N
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.59	.;N;.;.
REVEL	Benign	0.13
Sift	Pathogenic	0.0	.;D;.;.
Sift4G	Benign	0.10	.;T;.;.
Polyphen		0.98, 0.99	.;D;.;D
Vest4		0.27
MutPred		0.099		.;Gain of glycosylation at N66 (P = 0.0042);Gain of glycosylation at N66 (P = 0.0042);Gain of glycosylation at N66 (P = 0.0042);
MVP		0.48
MPC		0.30
ClinPred		0.69	D
GERP RS		2.4
Varity_R		0.34
gMVP		0.38

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: chr6-157099260;