rs558133631
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2
The NM_001283009.2(RTEL1):βc.2313_2315delβ(p.Glu771del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00523 in 1,610,860 control chromosomes in the GnomAD database, including 30 homozygotes. Variant has been reported in ClinVar as Likely benign (β β ).
Frequency
Genomes: π 0.0048 ( 3 hom., cov: 33)
Exomes π: 0.0053 ( 27 hom. )
Consequence
RTEL1
NM_001283009.2 inframe_deletion
NM_001283009.2 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.71
Genes affected
RTEL1 (HGNC:15888): (regulator of telomere elongation helicase 1) This gene encodes a DNA helicase which functions in the stability, protection and elongation of telomeres and interacts with proteins in the shelterin complex known to protect telomeres during DNA replication. Mutations in this gene have been associated with dyskeratosis congenita and Hoyerall-Hreidarsson syndrome. Read-through transcription of this gene into the neighboring downstream gene, which encodes tumor necrosis factor receptor superfamily, member 6b, generates a non-coding transcript. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]
RTEL1-TNFRSF6B (HGNC:44095): (RTEL1-TNFRSF6B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring RTEL1 (regulator of telomere elongation helicase 1) and TNFRSF6B (tumor necrosis factor receptor superfamily, member 6b, decoy) genes on chromosome 20. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_001283009.2. Strenght limited to Supporting due to length of the change: 1aa.
BP6
?
Variant 20-63690337-GAGA-G is Benign according to our data. Variant chr20-63690337-GAGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 436568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00483 (736/152298) while in subpopulation NFE AF= 0.00609 (414/68002). AF 95% confidence interval is 0.0056. There are 3 homozygotes in gnomad4. There are 378 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 3 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTEL1 | NM_001283009.2 | c.2313_2315del | p.Glu771del | inframe_deletion | 26/35 | ENST00000360203.11 | |
RTEL1-TNFRSF6B | NR_037882.1 | n.3140_3142del | non_coding_transcript_exon_variant | 26/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.2313_2315del | p.Glu771del | inframe_deletion | 26/35 | 5 | NM_001283009.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00484 AC: 737AN: 152180Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.00555 AC: 1379AN: 248682Hom.: 8 AF XY: 0.00538 AC XY: 726AN XY: 135034
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GnomAD4 exome AF: 0.00528 AC: 7695AN: 1458562Hom.: 27 AF XY: 0.00510 AC XY: 3701AN XY: 725464
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GnomAD4 genome ? AF: 0.00483 AC: 736AN: 152298Hom.: 3 Cov.: 33 AF XY: 0.00508 AC XY: 378AN XY: 74468
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | RTEL1: PM4:Supporting, BS2 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 28, 2015 | - - |
Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at