rs745463649
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_006509.4(RELB):c.1191C>A(p.Tyr397Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
RELB
NM_006509.4 stop_gained
NM_006509.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 2.57
Genes affected
RELB (HGNC:9956): (RELB proto-oncogene, NF-kB subunit) Enables RNA polymerase II cis-regulatory region sequence-specific DNA binding activity and protein kinase binding activity. Involved in lymphocyte differentiation and negative regulation of interferon-beta production. Located in cytosol and nucleoplasm. Part of chromatin; nucleus; and transcription repressor complex. Colocalizes with centrosome. Implicated in breast cancer and immunodeficiency 53. Biomarker of breast cancer and transitional cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-45032733-C-A is Pathogenic according to our data. Variant chr19-45032733-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 430895.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELB | NM_006509.4 | c.1191C>A | p.Tyr397Ter | stop_gained | 9/12 | ENST00000221452.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELB | ENST00000221452.13 | c.1191C>A | p.Tyr397Ter | stop_gained | 9/12 | 1 | NM_006509.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Immunodeficiency 53 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 29, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -4
Find out detailed SpliceAI scores and Pangolin per-transcript scores at