rs200803729
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001283009.2(RTEL1):c.1596-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 1,612,516 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0017 ( 9 hom., cov: 33)
Exomes 𝑓: 0.0032 ( 149 hom. )
Consequence
RTEL1
NM_001283009.2 splice_polypyrimidine_tract, intron
NM_001283009.2 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00002082
2
Clinical Significance
Conservation
PhyloP100: 0.184
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]
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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=-0.87).
BP6
?
Variant 20-63688130-C-T is Benign according to our data. Variant chr20-63688130-C-T is described in ClinVar as [Benign]. Clinvar id is 540966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00173 (264/152264) while in subpopulation SAS AF= 0.0498 (240/4820). AF 95% confidence interval is 0.0446. There are 9 homozygotes in gnomad4. There are 185 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 9 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTEL1 | NM_001283009.2 | c.1596-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000360203.11 | |||
RTEL1-TNFRSF6B | NR_037882.1 | n.2423-9C>T | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.1596-9C>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001283009.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00173 AC: 263AN: 152146Hom.: 9 Cov.: 33
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GnomAD3 exomes AF: 0.00658 AC: 1640AN: 249394Hom.: 55 AF XY: 0.00864 AC XY: 1170AN XY: 135460
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GnomAD4 exome AF: 0.00324 AC: 4724AN: 1460252Hom.: 149 Cov.: 45 AF XY: 0.00464 AC XY: 3373AN XY: 726400
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GnomAD4 genome ? AF: 0.00173 AC: 264AN: 152264Hom.: 9 Cov.: 33 AF XY: 0.00248 AC XY: 185AN XY: 74456
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Dyskeratosis congenita, autosomal recessive 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Counsyl | Dec 19, 2017 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 16, 2021 | - - |
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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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at