18-62325304-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The ENST00000269485(TNFRSF11A):c.-49G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000532 in 920,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000061 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000052 ( 0 hom. )
Consequence
TNFRSF11A
ENST00000269485 5_prime_UTR
ENST00000269485 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.55
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 Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000612 (9/147054) while in subpopulation AMR AF= 0.000135 (2/14788). AF 95% confidence interval is 0.0000385. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TNFRSF11A | NM_003839.4 | c.-49G>A | upstream_gene_variant | ENST00000586569.3 | NP_003830.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TNFRSF11A | ENST00000269485 | c.-49G>A | 5_prime_UTR_variant | 1/7 | 1 | ENSP00000269485.7 | ||||
TNFRSF11A | ENST00000586569.3 | c.-49G>A | upstream_gene_variant | 1 | NM_003839.4 | ENSP00000465500.1 | ||||
TNFRSF11A | ENST00000592013.1 | n.-22G>A | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000612 AC: 9AN: 147054Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000517 AC: 40AN: 773514Hom.: 0 Cov.: 11 AF XY: 0.0000580 AC XY: 21AN XY: 362088
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GnomAD4 genome AF: 0.0000612 AC: 9AN: 147054Hom.: 0 Cov.: 32 AF XY: 0.000112 AC XY: 8AN XY: 71538
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Bone Paget disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Osteopetrosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at