1-185300308-G-C
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_006469.5(IVNS1ABP):āc.1278C>Gā(p.His426Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,613,472 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00016 ( 0 hom., cov: 32)
Exomes š: 0.00018 ( 0 hom. )
Consequence
IVNS1ABP
NM_006469.5 missense
NM_006469.5 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 2.04
Genes affected
IVNS1ABP (HGNC:16951): (influenza virus NS1A binding protein) Involved in RNA splicing; negative regulation of protein ubiquitination; and response to virus. Located in cytosol. Implicated in immunodeficiency 70. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
Missense variant where missense usually causes diseases, IVNS1ABP
BS2
High AC in GnomAd4 at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IVNS1ABP | NM_006469.5 | c.1278C>G | p.His426Gln | missense_variant | 12/15 | ENST00000367498.8 | |
IVNS1ABP | XM_047434070.1 | c.1278C>G | p.His426Gln | missense_variant | 12/15 | ||
IVNS1ABP | XM_047434096.1 | c.1011C>G | p.His337Gln | missense_variant | 11/14 | ||
IVNS1ABP | XM_047434109.1 | c.624C>G | p.His208Gln | missense_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IVNS1ABP | ENST00000367498.8 | c.1278C>G | p.His426Gln | missense_variant | 12/15 | 1 | NM_006469.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000237 AC: 59AN: 248998Hom.: 0 AF XY: 0.000223 AC XY: 30AN XY: 134606
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GnomAD4 exome AF: 0.000180 AC: 263AN: 1461182Hom.: 0 Cov.: 33 AF XY: 0.000171 AC XY: 124AN XY: 726886
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GnomAD4 genome AF: 0.000158 AC: 24AN: 152290Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74458
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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 | Oct 26, 2022 | The c.1278C>G (p.H426Q) alteration is located in exon 12 (coding exon 10) of the IVNS1ABP gene. This alteration results from a C to G substitution at nucleotide position 1278, causing the histidine (H) at amino acid position 426 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D
M_CAP
Benign
D
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Loss of catalytic residue at D429 (P = 0.1607);
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