rs4149572
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_001065.4(TNFRSF1A):c.39+1199G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 152,066 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.025 ( 78 hom., cov: 32)
Consequence
TNFRSF1A
NM_001065.4 intron
NM_001065.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.152
Genes affected
TNFRSF1A (HGNC:11916): (TNF receptor superfamily member 1A) This gene encodes a member of the TNF receptor superfamily of proteins. The encoded receptor is found in membrane-bound and soluble forms that interact with membrane-bound and soluble forms, respectively, of its ligand, tumor necrosis factor alpha. Binding of membrane-bound tumor necrosis factor alpha to the membrane-bound receptor induces receptor trimerization and activation, which plays a role in cell survival, apoptosis, and inflammation. Proteolytic processing of the encoded receptor results in release of the soluble form of the receptor, which can interact with free tumor necrosis factor alpha to inhibit inflammation. Mutations in this gene underlie tumor necrosis factor receptor-associated periodic syndrome (TRAPS), characterized by fever, abdominal pain and other features. Mutations in this gene may also be associated with multiple sclerosis in human patients. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0252 (3838/152066) while in subpopulation NFE AF= 0.0357 (2427/67974). AF 95% confidence interval is 0.0345. There are 78 homozygotes in gnomad4. There are 1848 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 3838 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNFRSF1A | NM_001065.4 | c.39+1199G>T | intron_variant | ENST00000162749.7 | |||
TNFRSF1A | NM_001346091.2 | c.-132+1199G>T | intron_variant | ||||
TNFRSF1A | NM_001346092.2 | c.-539+1199G>T | intron_variant | ||||
TNFRSF1A | NR_144351.2 | n.301+1199G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFRSF1A | ENST00000162749.7 | c.39+1199G>T | intron_variant | 1 | NM_001065.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0253 AC: 3838AN: 151948Hom.: 78 Cov.: 32
GnomAD3 genomes
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.0252 AC: 3838AN: 152066Hom.: 78 Cov.: 32 AF XY: 0.0249 AC XY: 1848AN XY: 74332
GnomAD4 genome
?
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3838
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152066
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32
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1848
AN XY:
74332
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30
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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