dbSNP rs868142025: INO80B:p.Ala187Thr (chr2-74457352-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031288.4(INO80B):c.559G>A(p.Ala187Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,562 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A187S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

INO80B
NM_031288.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.17

Publications

0 publications found

Variant links:

Genes affected

INO80B (HGNC:13324): (INO80 complex subunit B) This gene encodes a subunit of an ATP-dependent chromatin remodeling complex, INO80, which plays a role in DNA and nucleosome-activated ATPase activity and ATP-dependent nucleosome sliding. Readthrough transcription of this gene into the neighboring downstream gene, which encodes WW domain-binding protein 1, generates a non-coding transcript. [provided by RefSeq, Feb 2011]

INO80B links:

INO80B-WBP1 (HGNC:49199): (INO80B-WBP1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring INO80B (INO80 complex subunit B) and WBP1 (WW domain-binding protein 1) genes on chromosome 2. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

INO80B-WBP1 links:

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ACMG classification

Classification was made for transcript

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=0.16937846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INO80B	NM_031288.4 link	c.559G>A	p.Ala187Thr	missense_variant	Exon 5 of 5	ENST00000233331.12	NP_112578.2	Q9C086
INO80B-WBP1	NR_037849.1 link	n.653G>A		non_coding_transcript_exon_variant	Exon 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INO80B	ENST00000233331.12 link	c.559G>A	p.Ala187Thr	missense_variant	Exon 5 of 5	1	NM_031288.4	ENSP00000233331.7		Q9C086
INO80B-WBP1	ENST00000452361.5 link	n.559G>A		non_coding_transcript_exon_variant	Exon 5 of 8	2		ENSP00000388677.1		J3KQ70

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455562

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723602

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33184

American (AMR)

AF:

0.00

AC:

AN:

44190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25942

East Asian (EAS)

AF:

0.00

AC:

AN:

39332

South Asian (SAS)

AF:

0.00

AC:

AN:

85176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109674

Other (OTH)

AF:

0.00

AC:

AN:

60114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;.;.

Eigen

Benign

0.032

Eigen_PC

Benign

0.096

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;.;.

PhyloP100

4.2

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.91

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.42

T;D;T

Sift4G

Benign

0.68

T;T;T

Polyphen

0.95

P;.;.

Vest4

0.22

MutPred

0.10

Gain of phosphorylation at A187 (P = 0.0409);.;.;

MVP

0.068

MPC

1.6

ClinPred

0.91

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.092

gMVP

0.16

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over