20-63659344-A-C

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.119
Variant links:
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

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RTEL1NM_001283009.2 linkc.-59A>C 5_prime_UTR_variant 2/35 ENST00000360203.11 NP_001269938.1 Q9NZ71-6R4IXY3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RTEL1ENST00000360203 linkc.-59A>C 5_prime_UTR_variant 2/355 NM_001283009.2 ENSP00000353332.5 Q9NZ71-6
RTEL1ENST00000508582 linkc.-59A>C 5_prime_UTR_variant 2/352 ENSP00000424307.2 Q9NZ71-7
RTEL1ENST00000370018 linkc.-59A>C 5_prime_UTR_variant 2/351 ENSP00000359035.3 Q9NZ71-1
RTEL1-TNFRSF6BENST00000492259.6 linkn.-59A>C non_coding_transcript_exon_variant 1/355 ENSP00000457428.1 D6RA96
RTEL1-TNFRSF6BENST00000492259.6 linkn.-59A>C 5_prime_UTR_variant 1/355 ENSP00000457428.1 D6RA96

Frequencies

GnomAD3 genomes
AF:
0.0386
AC:
5873
AN:
152122
Hom.:
172
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0111
Gnomad AMI
AF:
0.101
Gnomad AMR
AF:
0.0174
Gnomad ASJ
AF:
0.0242
Gnomad EAS
AF:
0.000577
Gnomad SAS
AF:
0.00850
Gnomad FIN
AF:
0.0596
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.0622
Gnomad OTH
AF:
0.0298
GnomAD4 exome
AF:
0.0557
AC:
65023
AN:
1168030
Hom.:
2197
Cov.:
16
AF XY:
0.0537
AC XY:
31875
AN XY:
593646
show subpopulations
Gnomad4 AFR exome
AF:
0.00875
Gnomad4 AMR exome
AF:
0.0143
Gnomad4 ASJ exome
AF:
0.0213
Gnomad4 EAS exome
AF:
0.000261
Gnomad4 SAS exome
AF:
0.00952
Gnomad4 FIN exome
AF:
0.0579
Gnomad4 NFE exome
AF:
0.0679
Gnomad4 OTH exome
AF:
0.0465
GnomAD4 genome
AF:
0.0386
AC:
5870
AN:
152240
Hom.:
172
Cov.:
33
AF XY:
0.0369
AC XY:
2748
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.0110
Gnomad4 AMR
AF:
0.0173
Gnomad4 ASJ
AF:
0.0242
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.00830
Gnomad4 FIN
AF:
0.0596
Gnomad4 NFE
AF:
0.0622
Gnomad4 OTH
AF:
0.0295
Alfa
AF:
0.0514
Hom.:
112
Bravo
AF:
0.0346
Asia WGS
AF:
0.00953
AC:
34
AN:
3478

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 submitterclinical testingGeneDxFeb 07, 2019- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
6.0
DANN
Benign
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs13043797; hg19: chr20-62290697; COSMIC: COSV58892799; COSMIC: COSV58892799; API