20-63659344-A-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001283009.2(RTEL1):c.-59A>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 0.0537 in 1,320,270 control chromosomes in the GnomAD database, including 2,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.039 ( 172 hom., cov: 33)
Exomes 𝑓: 0.056 ( 2197 hom. )
Consequence
RTEL1
NM_001283009.2 5_prime_UTR
NM_001283009.2 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.119
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 20-63659344-A-C is Benign according to our data. Variant chr20-63659344-A-C is described in ClinVar as [Benign]. Clinvar id is 1279544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63659344-A-C is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0606 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203 | c.-59A>C | 5_prime_UTR_variant | 2/35 | 5 | NM_001283009.2 | ENSP00000353332.5 | |||
RTEL1 | ENST00000508582 | c.-59A>C | 5_prime_UTR_variant | 2/35 | 2 | ENSP00000424307.2 | ||||
RTEL1 | ENST00000370018 | c.-59A>C | 5_prime_UTR_variant | 2/35 | 1 | ENSP00000359035.3 | ||||
RTEL1-TNFRSF6B | ENST00000492259.6 | n.-59A>C | non_coding_transcript_exon_variant | 1/35 | 5 | ENSP00000457428.1 | ||||
RTEL1-TNFRSF6B | ENST00000492259.6 | n.-59A>C | 5_prime_UTR_variant | 1/35 | 5 | ENSP00000457428.1 |
Frequencies
GnomAD3 genomes AF: 0.0386 AC: 5873AN: 152122Hom.: 172 Cov.: 33
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GnomAD4 exome AF: 0.0557 AC: 65023AN: 1168030Hom.: 2197 Cov.: 16 AF XY: 0.0537 AC XY: 31875AN XY: 593646
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GnomAD4 genome AF: 0.0386 AC: 5870AN: 152240Hom.: 172 Cov.: 33 AF XY: 0.0369 AC XY: 2748AN XY: 74424
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 07, 2019 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at