rs200803729

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 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 intron

Scores

2
Splicing: ADA: 0.00002082
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.184
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]

Genome browser will be placed here

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 Protein UniProt
RTEL1NM_001283009.2 linkuse as main transcriptc.1596-9C>T intron_variant ENST00000360203.11 NP_001269938.1 Q9NZ71-6R4IXY3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RTEL1ENST00000360203.11 linkuse as main transcriptc.1596-9C>T intron_variant 5 NM_001283009.2 ENSP00000353332.5 Q9NZ71-6
RTEL1ENST00000508582.7 linkuse as main transcriptc.1668-9C>T intron_variant 2 ENSP00000424307.2 Q9NZ71-7
RTEL1ENST00000370018.7 linkuse as main transcriptc.1596-9C>T intron_variant 1 ENSP00000359035.3 Q9NZ71-1
RTEL1-TNFRSF6BENST00000492259.6 linkuse as main transcriptn.1680-9C>T intron_variant 5 ENSP00000457428.1 D6RA96

Frequencies

GnomAD3 genomes
AF:
0.00173
AC:
263
AN:
152146
Hom.:
9
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.0495
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00318
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00658
AC:
1640
AN:
249394
Hom.:
55
AF XY:
0.00864
AC XY:
1170
AN XY:
135460
show subpopulations
Gnomad AFR exome
AF:
0.000187
Gnomad AMR exome
AF:
0.000203
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000490
Gnomad SAS exome
AF:
0.0519
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000116
Gnomad OTH exome
AF:
0.00345
GnomAD4 exome
AF:
0.00324
AC:
4724
AN:
1460252
Hom.:
149
Cov.:
45
AF XY:
0.00464
AC XY:
3373
AN XY:
726400
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000252
Gnomad4 SAS exome
AF:
0.0499
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000121
Gnomad4 OTH exome
AF:
0.00406
GnomAD4 genome
AF:
0.00173
AC:
264
AN:
152264
Hom.:
9
Cov.:
33
AF XY:
0.00248
AC XY:
185
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000579
Gnomad4 SAS
AF:
0.0498
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000246
Hom.:
0
Bravo
AF:
0.000476
Asia WGS
AF:
0.0260
AC:
89
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000237

ClinVar

Significance: 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 submitterclinical testingGeneDxApr 16, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Dyskeratosis congenita, autosomal recessive 5 Benign:1
Benign, criteria provided, single submitterclinical testingCounsylDec 19, 2017- -
Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
7.5
DANN
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000021
dbscSNV1_RF
Benign
0.0
SpliceAI score (max)
0.010
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: rs200803729; hg19: chr20-62319483; API