rs2277438
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_003701.4(TNFSF11):c.220-94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 1,337,336 control chromosomes in the GnomAD database, including 449,893 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.81 ( 49688 hom., cov: 32)
Exomes 𝑓: 0.82 ( 400205 hom. )
Consequence
TNFSF11
NM_003701.4 intron
NM_003701.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.40
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 13-42581032-G-A is Benign according to our data. Variant chr13-42581032-G-A is described in ClinVar as [Benign]. Clinvar id is 1183681.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNFSF11 | NM_003701.4 | c.220-94G>A | intron_variant | ENST00000398795.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFSF11 | ENST00000398795.7 | c.220-94G>A | intron_variant | 1 | NM_003701.4 | P1 | |||
TNFSF11 | ENST00000358545.6 | c.1-94G>A | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.807 AC: 122660AN: 152076Hom.: 49654 Cov.: 32
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GnomAD4 exome AF: 0.820 AC: 971627AN: 1185142Hom.: 400205 AF XY: 0.824 AC XY: 496768AN XY: 603196
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GnomAD4 genome ? AF: 0.806 AC: 122742AN: 152194Hom.: 49688 Cov.: 32 AF XY: 0.808 AC XY: 60118AN XY: 74402
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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 | GeneDx | Nov 12, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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