2-74457470-A-T

Variant summary

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

The NM_031288.4(INO80B):​c.677A>T​(p.Gln226Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,318 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

INO80B
NM_031288.4 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.50

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-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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
INO80BNM_031288.4 linkc.677A>T p.Gln226Leu missense_variant Exon 5 of 5 ENST00000233331.12 NP_112578.2 Q9C086
INO80B-WBP1NR_037849.1 linkn.771A>T non_coding_transcript_exon_variant Exon 5 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
INO80BENST00000233331.12 linkc.677A>T p.Gln226Leu missense_variant Exon 5 of 5 1 NM_031288.4 ENSP00000233331.7 Q9C086
INO80B-WBP1ENST00000452361.5 linkn.677A>T non_coding_transcript_exon_variant Exon 5 of 8 2 ENSP00000388677.1 J3KQ70

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
158108
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.11e-7
AC:
1
AN:
1406318
Hom.:
0
Cov.:
32
AF XY:
0.00000144
AC XY:
1
AN XY:
694902
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31924
American (AMR)
AF:
0.00
AC:
0
AN:
36896
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25192
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36290
South Asian (SAS)
AF:
0.00
AC:
0
AN:
80278
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
47958
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5686
European-Non Finnish (NFE)
AF:
9.23e-7
AC:
1
AN:
1083796
Other (OTH)
AF:
0.00
AC:
0
AN:
58298
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 17, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.677A>T (p.Q226L) alteration is located in exon 5 (coding exon 5) of the INO80B gene. This alteration results from a A to T substitution at nucleotide position 677, causing the glutamine (Q) at amino acid position 226 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
0.0060
T
BayesDel_noAF
Benign
-0.23
CADD
Pathogenic
26
DANN
Benign
0.94
DEOGEN2
Benign
0.34
T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.87
D
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.58
D
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.6
L
PhyloP100
8.5
PrimateAI
Uncertain
0.79
T
PROVEAN
Uncertain
-2.9
D
REVEL
Uncertain
0.35
Sift
Benign
0.13
T
Sift4G
Benign
1.0
T
Polyphen
0.99
D
Vest4
0.62
MutPred
0.49
Gain of methylation at K222 (P = 0.2185);
MVP
0.20
MPC
1.6
ClinPred
0.99
D
GERP RS
4.6
Varity_R
0.42
gMVP
0.73
Mutation Taster
=49/51
disease causing

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

Other links and lift over

dbSNP: rs1375758975; hg19: chr2-74684597; API