1-12192919-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001066.3(TNFRSF1B):c.608C>T(p.Thr203Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000647 in 1,614,182 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00047 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00067 ( 14 hom. )
Consequence
TNFRSF1B
NM_001066.3 missense
NM_001066.3 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: -1.11
Genes affected
TNFRSF1B (HGNC:11917): (TNF receptor superfamily member 1B) The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein and TNF-receptor 1 form a heterocomplex that mediates the recruitment of two anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. The function of IAPs in TNF-receptor signalling is unknown, however, c-IAP1 is thought to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2, which mediates anti-apoptotic signals. Knockout studies in mice also suggest a role of this protein in protecting neurons from apoptosis by stimulating antioxidative pathways. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.00282982).
BP6
?
Variant 1-12192919-C-T is Benign according to our data. Variant chr1-12192919-C-T is described in ClinVar as [Benign]. Clinvar id is 744556.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAdExome at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNFRSF1B | NM_001066.3 | c.608C>T | p.Thr203Met | missense_variant | 6/10 | ENST00000376259.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFRSF1B | ENST00000376259.7 | c.608C>T | p.Thr203Met | missense_variant | 6/10 | 1 | NM_001066.3 | P1 | |
TNFRSF1B | ENST00000492361.1 | n.597C>T | non_coding_transcript_exon_variant | 5/9 | 1 | ||||
TNFRSF1B | ENST00000489921.1 | n.320C>T | non_coding_transcript_exon_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000460 AC: 70AN: 152188Hom.: 1 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00130 AC: 326AN: 251100Hom.: 2 AF XY: 0.00165 AC XY: 224AN XY: 135728
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GnomAD4 exome AF: 0.000666 AC: 973AN: 1461876Hom.: 14 Cov.: 34 AF XY: 0.000892 AC XY: 649AN XY: 727238
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GnomAD4 genome ? AF: 0.000473 AC: 72AN: 152306Hom.: 1 Cov.: 33 AF XY: 0.000698 AC XY: 52AN XY: 74478
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 21, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
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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