NM_001283009.2:c.2112C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001283009.2(RTEL1):c.2112C>T(p.Asp704Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 1,610,866 control chromosomes in the GnomAD database, including 6,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 419 hom., cov: 33)

Exomes 𝑓: 0.083 ( 5655 hom. )

Consequence

RTEL1
NM_001283009.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 0.634

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 links:

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]

RTEL1-TNFRSF6B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 20-63689836-C-T is Benign according to our data. Variant chr20-63689836-C-T is described in ClinVar as [Benign]. Clinvar id is 403399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63689836-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.634 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTEL1	NM_001283009.2 link	c.2112C>T	p.Asp704Asp	synonymous_variant	Exon 24 of 35	ENST00000360203.11	NP_001269938.1	Q9NZ71-6R4IXY3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RTEL1	ENST00000360203.11 link	c.2112C>T	p.Asp704Asp	synonymous_variant	Exon 24 of 35	5	NM_001283009.2	ENSP00000353332.5	Q9NZ71-6
RTEL1	ENST00000508582.7 link	c.2184C>T	p.Asp728Asp	synonymous_variant	Exon 24 of 35	2		ENSP00000424307.2	Q9NZ71-7
RTEL1	ENST00000370018.7 link	c.2112C>T	p.Asp704Asp	synonymous_variant	Exon 24 of 35	1		ENSP00000359035.3	Q9NZ71-1
RTEL1-TNFRSF6B	ENST00000492259.6 link	n.2196C>T		non_coding_transcript_exon_variant	Exon 22 of 35	5		ENSP00000457428.1	D6RA96

Frequencies

GnomAD3 genomes

AF:

0.0666

AC:

10130

AN:

152142

Hom.:

420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0165

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0796

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0809

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.0904

Gnomad OTH

AF:

0.0842

GnomAD3 exomes

AF:

0.0791

AC:

19445

AN:

245828

Hom.:

1007

AF XY:

0.0845

AC XY:

11317

AN XY:

133910

show subpopulations

Gnomad AFR exome

AF:

0.0130

Gnomad AMR exome

AF:

0.0572

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.000273

Gnomad SAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.0850

Gnomad NFE exome

AF:

0.0914

Gnomad OTH exome

AF:

0.0959

GnomAD4 exome

AF:

0.0834

AC:

121616

AN:

1458606

Hom.:

5655

Cov.:

AF XY:

0.0859

AC XY:

62320

AN XY:

725660

show subpopulations

Gnomad4 AFR exome

AF:

0.0146

Gnomad4 AMR exome

AF:

0.0608

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.123

Gnomad4 FIN exome

AF:

0.0850

Gnomad4 NFE exome

AF:

0.0850

Gnomad4 OTH exome

AF:

0.0829

GnomAD4 genome

AF:

0.0665

AC:

10132

AN:

152260

Hom.:

419

Cov.:

AF XY:

0.0671

AC XY:

4999

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0165

Gnomad4 AMR

AF:

0.0795

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.122

Gnomad4 FIN

AF:

0.0809

Gnomad4 NFE

AF:

0.0904

Gnomad4 OTH

AF:

0.0833

Alfa

AF:

0.0825

Hom.:

323

Bravo

AF:

0.0610

Asia WGS

AF:

0.0450

AC:

156

AN:

3478

EpiCase

AF:

0.0951

EpiControl

AF:

0.0984

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 15, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Dyskeratosis congenita, autosomal recessive 5

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dyskeratosis congenita

Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over