rs863223356
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_021975.4(RELA):āc.329T>Cā(p.Ile110Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I110M) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RELA
NM_021975.4 missense
NM_021975.4 missense
Scores
3
5
11
Clinical Significance
Conservation
PhyloP100: 6.97
Genes affected
RELA (HGNC:9955): (RELA proto-oncogene, NF-kB subunit) NF-kappa-B is a ubiquitous transcription factor involved in several biological processes. It is held in the cytoplasm in an inactive state by specific inhibitors. Upon degradation of the inhibitor, NF-kappa-B moves to the nucleus and activates transcription of specific genes. NF-kappa-B is composed of NFKB1 or NFKB2 bound to either REL, RELA, or RELB. The most abundant form of NF-kappa-B is NFKB1 complexed with the product of this gene, RELA. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 11-65661693-A-G is Pathogenic according to our data. Variant chr11-65661693-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 208401.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-65661693-A-G is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELA | NM_021975.4 | c.329T>C | p.Ile110Thr | missense_variant | 4/11 | ENST00000406246.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELA | ENST00000406246.8 | c.329T>C | p.Ile110Thr | missense_variant | 4/11 | 1 | NM_021975.4 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1438452Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 713322
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1438452
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
713322
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Childhood-onset schizophrenia Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Dr. Guy Rouleau's laboratory, McGill University | Jan 01, 2014 | COS with Asperger's Disorder - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;.;T;.;T;.;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.;N;.;.;.;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;.;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;.;.;T;T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;.;.;.;.;.;.
Polyphen
P;.;.;B;P;.;.;.;.;.;.
Vest4
MutPred
Loss of stability (P = 0.0322);Loss of stability (P = 0.0322);Loss of stability (P = 0.0322);Loss of stability (P = 0.0322);Loss of stability (P = 0.0322);.;.;.;Loss of stability (P = 0.0322);.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at