rs9594782
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_003701.4(TNFSF11):c.219+2528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 152,326 control chromosomes in the GnomAD database, including 182 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 0.042 ( 182 hom., cov: 33)
Consequence
TNFSF11
NM_003701.4 intron
NM_003701.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.693
Genes affected
TNFSF11 (HGNC:11926): (TNF superfamily member 11) This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of this gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which indicated this protein may have a role in the regulation of cell apoptosis. Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. Two alternatively spliced transcript variants have been found. [provided by RefSeq, Jul 2008]
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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=-0.86).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0849 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNFSF11 | NM_003701.4 | c.219+2528T>C | intron_variant | ENST00000398795.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFSF11 | ENST00000398795.7 | c.219+2528T>C | intron_variant | 1 | NM_003701.4 | P1 | |||
TNFSF11 | ENST00000358545.6 | c.1-4076T>C | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0417 AC: 6342AN: 152208Hom.: 180 Cov.: 33
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: 0.0417 AC: 6347AN: 152326Hom.: 182 Cov.: 33 AF XY: 0.0410 AC XY: 3052AN XY: 74486
GnomAD4 genome
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33
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3052
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74486
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264
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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