chr2-74457563-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_031288.4(INO80B):c.770C>T(p.Ala257Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000547 in 1,516,868 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00032 ( 2 hom., cov: 33)
Exomes 𝑓: 0.000026 ( 0 hom. )
Consequence
INO80B
NM_031288.4 missense
NM_031288.4 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 2.53
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.033274293).
BS2
?
High Homozygotes in GnomAd at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INO80B | NM_031288.4 | c.770C>T | p.Ala257Val | missense_variant | 5/5 | ENST00000233331.12 | |
INO80B-WBP1 | NR_037849.1 | n.864C>T | non_coding_transcript_exon_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INO80B | ENST00000233331.12 | c.770C>T | p.Ala257Val | missense_variant | 5/5 | 1 | NM_031288.4 | P1 | |
INO80B | ENST00000409917.5 | c.*127C>T | 3_prime_UTR_variant | 5/5 | 2 | ||||
INO80B | ENST00000469849.1 | n.577C>T | non_coding_transcript_exon_variant | 4/4 | 5 | ||||
INO80B | ENST00000455562.1 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000315 AC: 48AN: 152180Hom.: 2 Cov.: 33
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?
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GnomAD3 exomes AF: 0.000196 AC: 22AN: 112102Hom.: 0 AF XY: 0.000129 AC XY: 8AN XY: 61972
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GnomAD4 exome AF: 0.0000256 AC: 35AN: 1364688Hom.: 0 Cov.: 33 AF XY: 0.0000193 AC XY: 13AN XY: 672248
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 07, 2023 | The c.770C>T (p.A257V) alteration is located in exon 5 (coding exon 5) of the INO80B gene. This alteration results from a C to T substitution at nucleotide position 770, causing the alanine (A) at amino acid position 257 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Gain of sheet (P = 0.0344);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at