6-31577312-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_000594.4(TNF):c.477C>T(p.Ile159Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,613,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000074 ( 0 hom. )
Consequence
TNF
NM_000594.4 synonymous
NM_000594.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.75
Genes affected
TNF (HGNC:11892): (tumor necrosis factor) This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, psoriasis, rheumatoid arthritis ankylosing spondylitis, tuberculosis, autosomal dominant polycystic kidney disease, and cancer. Mutations in this gene affect susceptibility to cerebral malaria, septic shock, and Alzheimer disease. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 6-31577312-C-T is Benign according to our data. Variant chr6-31577312-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 723481.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-3.75 with no splicing effect.
BS2
High AC in GnomAd4 at 56 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TNF | ENST00000449264.3 | c.477C>T | p.Ile159Ile | synonymous_variant | 4/4 | 1 | NM_000594.4 | ENSP00000398698.2 | ||
TNF | ENST00000699334.1 | c.*209C>T | 3_prime_UTR_variant | 3/3 | ENSP00000514308.1 |
Frequencies
GnomAD3 genomes AF: 0.000368 AC: 56AN: 152236Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000688 AC: 17AN: 247078Hom.: 0 AF XY: 0.0000743 AC XY: 10AN XY: 134576
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GnomAD4 exome AF: 0.0000739 AC: 108AN: 1460890Hom.: 0 Cov.: 31 AF XY: 0.0000647 AC XY: 47AN XY: 726752
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GnomAD4 genome AF: 0.000368 AC: 56AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32AN XY: 74372
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 28, 2018 | - - |
Computational scores
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Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at