rs1564858
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002546.4(TNFRSF11B):c.400+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,613,884 control chromosomes in the GnomAD database, including 12,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.099 ( 865 hom., cov: 32)
Exomes 𝑓: 0.12 ( 11749 hom. )
Consequence
TNFRSF11B
NM_002546.4 splice_donor_region, intron
NM_002546.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0004132
2
Clinical Significance
Conservation
PhyloP100: -1.80
Genes affected
TNFRSF11B (HGNC:11909): (TNF receptor superfamily member 11b) The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein is an osteoblast-secreted decoy receptor that functions as a negative regulator of bone resorption. This protein specifically binds to its ligand, osteoprotegerin ligand, both of which are key extracellular regulators of osteoclast development. Studies of the mouse counterpart also suggest that this protein and its ligand play a role in lymph-node organogenesis and vascular calcification. Alternatively spliced transcript variants of this gene have been reported, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
?
Variant 8-118932927-G-A is Benign according to our data. Variant chr8-118932927-G-A is described in ClinVar as [Benign]. Clinvar id is 258772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNFRSF11B | NM_002546.4 | c.400+4C>T | splice_donor_region_variant, intron_variant | ENST00000297350.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFRSF11B | ENST00000297350.9 | c.400+4C>T | splice_donor_region_variant, intron_variant | 1 | NM_002546.4 | P1 | |||
TNFRSF11B | ENST00000517352.1 | c.400+4C>T | splice_donor_region_variant, intron_variant, NMD_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0986 AC: 15001AN: 152086Hom.: 865 Cov.: 32
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GnomAD3 exomes AF: 0.105 AC: 26347AN: 250686Hom.: 1719 AF XY: 0.110 AC XY: 14951AN XY: 135682
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GnomAD4 exome AF: 0.122 AC: 178393AN: 1461680Hom.: 11749 Cov.: 32 AF XY: 0.123 AC XY: 89342AN XY: 727154
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GnomAD4 genome ? AF: 0.0986 AC: 15014AN: 152204Hom.: 865 Cov.: 32 AF XY: 0.0968 AC XY: 7204AN XY: 74416
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Hyperphosphatasemia with bone disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at