rs6011020

Variant names:

• chr20-63673960-G-A
• rs6011020
• NM_001283009.2:c.786G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001283009.2(RTEL1):​c.786G>A​(p.Ser262Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00903 in 1,612,716 control chromosomes in the GnomAD database, including 1,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S262S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.048 (584 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (540 hom.)
• Consequence: RTEL1 NM_001283009.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.94
• Publications: 1 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]

LOC124904954 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 20-63673960-G-A is Benign according to our data. Variant chr20-63673960-G-A is described in ClinVar as Benign. ClinVar VariationId is 473924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.94 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTEL1	NM_001283009.2	MANE Select	c.786G>A	p.Ser262Ser	synonymous	Exon 10 of 35	NP_001269938.1
	RTEL1	NM_032957.5		c.858G>A	p.Ser286Ser	synonymous	Exon 10 of 35	NP_116575.3
	RTEL1	NM_016434.4		c.786G>A	p.Ser262Ser	synonymous	Exon 10 of 35	NP_057518.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTEL1	ENST00000360203.11	TSL:5 MANE Select	c.786G>A	p.Ser262Ser	synonymous	Exon 10 of 35	ENSP00000353332.5
	RTEL1	ENST00000508582.7	TSL:2	c.858G>A	p.Ser286Ser	synonymous	Exon 10 of 35	ENSP00000424307.2
	RTEL1	ENST00000370018.7	TSL:1	c.786G>A	p.Ser262Ser	synonymous	Exon 10 of 35	ENSP00000359035.3

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7245 AN: 152054 Hom.: 579 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0278

GnomAD2 exomes AF: 0.0124 AC: 3113 AN: 250610 AF XY: 0.00901

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.00728

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000653

Gnomad OTH exome AF: 0.00507

GnomAD4 exome AF: 0.00499 AC: 7290 AN: 1460544 Hom.: 540 Cov.: 32 AF XY: 0.00423 AC XY: 3070 AN XY: 726462

African (AFR) AF: 0.172 AC: 5741 AN: 33450

American (AMR) AF: 0.00814 AC: 363 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39668

South Asian (SAS) AF: 0.000302 AC: 26 AN: 86150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00850 AC: 49 AN: 5764

European-Non Finnish (NFE) AF: 0.000418 AC: 464 AN: 1111136

Other (OTH) AF: 0.0107 AC: 646 AN: 60344

GnomAD4 genome AF: 0.0478 AC: 7276 AN: 152172 Hom.: 584 Cov.: 32 AF XY: 0.0466 AC XY: 3464 AN XY: 74386

African (AFR) AF: 0.167 AC: 6918 AN: 41468

American (AMR) AF: 0.0160 AC: 244 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68014

Other (OTH) AF: 0.0275 AC: 58 AN: 2106

Alfa AF: 0.0261 Hom.: 170

Bravo AF: 0.0538

Asia WGS AF: 0.00982 AC: 35 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.00107

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Oct 17, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Mar 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.70
PhyloP100		-2.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs6011020; hg19: chr20-62305313;