rs1800693
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001065.4(TNFRSF1A):c.625+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,611,606 control chromosomes in the GnomAD database, including 123,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.38 ( 10910 hom., cov: 30)
Exomes 𝑓: 0.39 ( 112398 hom. )
Consequence
TNFRSF1A
NM_001065.4 intron
NM_001065.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.172
Genes affected
TNFRSF1A (HGNC:11916): (TNF receptor superfamily member 1A) This gene encodes a member of the TNF receptor superfamily of proteins. The encoded receptor is found in membrane-bound and soluble forms that interact with membrane-bound and soluble forms, respectively, of its ligand, tumor necrosis factor alpha. Binding of membrane-bound tumor necrosis factor alpha to the membrane-bound receptor induces receptor trimerization and activation, which plays a role in cell survival, apoptosis, and inflammation. Proteolytic processing of the encoded receptor results in release of the soluble form of the receptor, which can interact with free tumor necrosis factor alpha to inhibit inflammation. Mutations in this gene underlie tumor necrosis factor receptor-associated periodic syndrome (TRAPS), characterized by fever, abdominal pain and other features. Mutations in this gene may also be associated with multiple sclerosis in human patients. [provided by RefSeq, Sep 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 12-6330843-T-C is Benign according to our data. Variant chr12-6330843-T-C is described in ClinVar as [Benign]. Clinvar id is 37038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-6330843-T-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TNFRSF1A | NM_001065.4 | c.625+10A>G | intron_variant | ENST00000162749.7 | NP_001056.1 | |||
TNFRSF1A | NM_001346091.2 | c.301+10A>G | intron_variant | NP_001333020.1 | ||||
TNFRSF1A | NM_001346092.2 | c.166+10A>G | intron_variant | NP_001333021.1 | ||||
TNFRSF1A | NR_144351.2 | n.814-132A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TNFRSF1A | ENST00000162749.7 | c.625+10A>G | intron_variant | 1 | NM_001065.4 | ENSP00000162749 | P1 |
Frequencies
GnomAD3 genomes AF: 0.375 AC: 56939AN: 151700Hom.: 10912 Cov.: 30
GnomAD3 genomes
AF:
AC:
56939
AN:
151700
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.361 AC: 90633AN: 251114Hom.: 17154 AF XY: 0.361 AC XY: 49021AN XY: 135750
GnomAD3 exomes
AF:
AC:
90633
AN:
251114
Hom.:
AF XY:
AC XY:
49021
AN XY:
135750
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.388 AC: 566393AN: 1459786Hom.: 112398 Cov.: 33 AF XY: 0.387 AC XY: 281181AN XY: 726316
GnomAD4 exome
AF:
AC:
566393
AN:
1459786
Hom.:
Cov.:
33
AF XY:
AC XY:
281181
AN XY:
726316
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.375 AC: 56939AN: 151820Hom.: 10910 Cov.: 30 AF XY: 0.374 AC XY: 27718AN XY: 74180
GnomAD4 genome
AF:
AC:
56939
AN:
151820
Hom.:
Cov.:
30
AF XY:
AC XY:
27718
AN XY:
74180
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
800
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Uncertain:3Benign:11Other:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Nov 12, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 55% of patients studied by a panel of primary immunodeficiencies. Number of patients: 53. Only high quality variants are reported. - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
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, one paper claims association with MS - |
not provided Benign:3Other:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 24174586, 22801493, 23624563) - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
TNF receptor-associated periodic fever syndrome (TRAPS) Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Associated with severe COVID-19 disease Uncertain:1
Uncertain significance, no assertion criteria provided | research | HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas | Jul 01, 2023 | - - |
Susceptibility to severe coronavirus disease (COVID-19) Uncertain:1
Uncertain significance, no assertion criteria provided | research | HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas | Feb 09, 2021 | - - |
Susceptibility to severe coronavirus disease (COVID-19) due to high plasma levels of TNF, TNFR, and/or TNFR6 Uncertain:1
Uncertain significance, no assertion criteria provided | research | HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas | Aug 07, 2021 | NA - |
Autoinflammatory syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jan 14, 2022 | - - |
Multiple sclerosis, susceptibility to, 5 Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Aug 23, 2012 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at