chr9-136921160-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_021138.4(TRAF2):c.1083C>T(p.Phe361=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,613,904 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.013 ( 43 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 37 hom. )
Consequence
TRAF2
NM_021138.4 synonymous
NM_021138.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.08
Genes affected
TRAF2 (HGNC:12032): (TNF receptor associated factor 2) The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms a heterodimeric complex with TRAF1. This protein is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF1 interacts with the inhibitor-of-apoptosis proteins (IAPs), and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. BIRC2/c-IAP1, an apoptosis inhibitor possessing ubiquitin ligase activity, can unbiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
?
Variant 9-136921160-C-T is Benign according to our data. Variant chr9-136921160-C-T is described in ClinVar as [Benign]. Clinvar id is 783563.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.08 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0132 (2009/152268) while in subpopulation AFR AF= 0.0459 (1908/41530). AF 95% confidence interval is 0.0442. There are 43 homozygotes in gnomad4. There are 956 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 2006 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRAF2 | NM_021138.4 | c.1083C>T | p.Phe361= | synonymous_variant | 9/11 | ENST00000247668.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAF2 | ENST00000247668.7 | c.1083C>T | p.Phe361= | synonymous_variant | 9/11 | 1 | NM_021138.4 | P1 | |
TRAF2 | ENST00000466107.1 | n.36C>T | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0132 AC: 2006AN: 152150Hom.: 43 Cov.: 33
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GnomAD3 exomes AF: 0.00335 AC: 841AN: 251122Hom.: 11 AF XY: 0.00245 AC XY: 333AN XY: 135872
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GnomAD4 exome AF: 0.00140 AC: 2043AN: 1461636Hom.: 37 Cov.: 31 AF XY: 0.00122 AC XY: 888AN XY: 727124
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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 | Apr 24, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at