rs1805033
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_003839.4(TNFRSF11A):c.-9T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,015,216 control chromosomes in the GnomAD database, including 37,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.28 ( 6061 hom., cov: 31)
Exomes 𝑓: 0.27 ( 31872 hom. )
Consequence
TNFRSF11A
NM_003839.4 5_prime_UTR
NM_003839.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0360
Genes affected
TNFRSF11A (HGNC:11908): (TNF receptor superfamily member 11a) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptors can interact with various TRAF family proteins, through which this receptor induces the activation of NF-kappa B and MAPK8/JNK. This receptor and its ligand are important regulators of the interaction between T cells and dendritic cells. This receptor is also an essential mediator for osteoclast and lymph node development. Mutations at this locus have been associated with familial expansile osteolysis, autosomal recessive osteopetrosis, and Paget disease of bone. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Aug 2012]
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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=-0.85).
BP6
Variant 18-62325344-T-C is Benign according to our data. Variant chr18-62325344-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 193259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNFRSF11A | NM_003839.4 | c.-9T>C | 5_prime_UTR_variant | 1/10 | ENST00000586569.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFRSF11A | ENST00000586569.3 | c.-9T>C | 5_prime_UTR_variant | 1/10 | 1 | NM_003839.4 | P2 | ||
TNFRSF11A | ENST00000269485.11 | c.-9T>C | 5_prime_UTR_variant | 1/7 | 1 | A2 | |||
TNFRSF11A | ENST00000592013.1 | n.19T>C | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.279 AC: 40887AN: 146526Hom.: 6058 Cov.: 31
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GnomAD3 exomes AF: 0.141 AC: 863AN: 6136Hom.: 61 AF XY: 0.133 AC XY: 465AN XY: 3500
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GnomAD4 exome AF: 0.267 AC: 231875AN: 868590Hom.: 31872 Cov.: 26 AF XY: 0.266 AC XY: 108782AN XY: 408986
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GnomAD4 genome AF: 0.279 AC: 40902AN: 146626Hom.: 6061 Cov.: 31 AF XY: 0.274 AC XY: 19579AN XY: 71374
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 14, 2018 | - - |
Bone Paget disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2021 | - - |
Osteopetrosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at