rs200008996

Variant names:

• chr20-63685513-TG-T
• rs200008996
• NM_001283009.2:c.1192-9delG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001283009.2(RTEL1):​c.1192-9delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,612,132 control chromosomes in the GnomAD database, including 62 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (29 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (33 hom.)
• Consequence: RTEL1 NM_001283009.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.178
• Publications: 0 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]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 20-63685513-TG-T is Benign according to our data. Variant chr20-63685513-TG-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 473903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0105 (1601/152274) while in subpopulation AFR AF = 0.0368 (1528/41544). AF 95% confidence interval is 0.0352. There are 29 homozygotes in GnomAd4. There are 741 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTEL1	NM_001283009.2	c.1192-9delG		intron_variant	Intron 14 of 34	ENST00000360203.11	NP_001269938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTEL1	ENST00000360203.11	c.1192-9delG		intron_variant	Intron 14 of 34	5	NM_001283009.2	ENSP00000353332.5
RTEL1	ENST00000508582.7	c.1264-9delG		intron_variant	Intron 14 of 34	2		ENSP00000424307.2
RTEL1	ENST00000370018.7	c.1192-9delG		intron_variant	Intron 14 of 34	1		ENSP00000359035.3
RTEL1-TNFRSF6B	ENST00000492259.6	n.1276-9delG		intron_variant	Intron 12 of 34	5		ENSP00000457428.1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1599 AN: 152156 Hom.: 29 Cov.: 33

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00265 AC: 657 AN: 247556 AF XY: 0.00176

Gnomad AFR exome AF: 0.0370

Gnomad AMR exome AF: 0.00157

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000359

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.00108 AC: 1580 AN: 1459858 Hom.: 33 Cov.: 32 AF XY: 0.000859 AC XY: 624 AN XY: 726116

African (AFR) AF: 0.0392 AC: 1312 AN: 33460

American (AMR) AF: 0.00170 AC: 76 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52204

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5764

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111718

Other (OTH) AF: 0.00255 AC: 154 AN: 60324

GnomAD4 genome AF: 0.0105 AC: 1601 AN: 152274 Hom.: 29 Cov.: 33 AF XY: 0.00995 AC XY: 741 AN XY: 74452

African (AFR) AF: 0.0368 AC: 1528 AN: 41544

American (AMR) AF: 0.00327 AC: 50 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68006

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.000524 Hom.: 0

Bravo AF: 0.0125

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Mar 23, 2021

GeneDx

Significance: Likely 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

- -

RTEL1-related disorder Benign:1

Jul 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Dyskeratosis congenita Benign:1

Sep 27, 2019

Natera, Inc.

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs200008996; hg19: chr20-62316866;