NM_001283009.2:c.1548C>A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_001283009.2(RTEL1):c.1548C>A(p.Val516Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,470 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. V516V) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
RTEL1
NM_001283009.2 synonymous
NM_001283009.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.309
Publications
2 publications found
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 was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 20-63688003-C-A is Benign according to our data. Variant chr20-63688003-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2928633.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001283009.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RTEL1 | NM_001283009.2 | MANE Select | c.1548C>A | p.Val516Val | synonymous | Exon 18 of 35 | NP_001269938.1 | ||
| RTEL1 | NM_032957.5 | c.1620C>A | p.Val540Val | synonymous | Exon 18 of 35 | NP_116575.3 | |||
| RTEL1 | NM_016434.4 | c.1548C>A | p.Val516Val | synonymous | Exon 18 of 35 | NP_057518.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RTEL1 | ENST00000360203.11 | TSL:5 MANE Select | c.1548C>A | p.Val516Val | synonymous | Exon 18 of 35 | ENSP00000353332.5 | ||
| RTEL1 | ENST00000508582.7 | TSL:2 | c.1620C>A | p.Val540Val | synonymous | Exon 18 of 35 | ENSP00000424307.2 | ||
| RTEL1 | ENST00000370018.7 | TSL:1 | c.1548C>A | p.Val516Val | synonymous | Exon 18 of 35 | ENSP00000359035.3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000802 AC: 2AN: 249444 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
249444
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460470Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726522 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1460470
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
726522
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
2
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
52074
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111964
Other (OTH)
AF:
AC:
0
AN:
60376
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
Variant carriers
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GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
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Bravo
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ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (1)
-
-
1
RTEL1-related disorder (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
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
Publications
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