rs79210260

Variant names:

• chr20-63689576-C-T
• rs79210260
• NM_001283009.2:c.1953C>T

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.1953C>T​(p.Arg651Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00417 in 1,612,290 control chromosomes in the GnomAD database, including 255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (27 hom., cov: 33)
  • Exomes 𝑓: 0.0040 (228 hom.)
• Consequence: RTEL1 NM_001283009.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0570
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 20-63689576-C-T is Benign according to our data. Variant chr20-63689576-C-T is described in ClinVar as Benign. ClinVar VariationId is 473911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.057 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0903 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTEL1	NM_001283009.2	MANE Select	c.1953C>T	p.Arg651Arg	synonymous	Exon 23 of 35	NP_001269938.1	Q9NZ71-6
	RTEL1	NM_032957.5		c.2025C>T	p.Arg675Arg	synonymous	Exon 23 of 35	NP_116575.3	Q9NZ71-7
	RTEL1	NM_016434.4		c.1953C>T	p.Arg651Arg	synonymous	Exon 23 of 35	NP_057518.1	Q9NZ71-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTEL1	ENST00000360203.11	TSL:5 MANE Select	c.1953C>T	p.Arg651Arg	synonymous	Exon 23 of 35	ENSP00000353332.5	Q9NZ71-6
	RTEL1	ENST00000508582.7	TSL:2	c.2025C>T	p.Arg675Arg	synonymous	Exon 23 of 35	ENSP00000424307.2	Q9NZ71-7
	RTEL1	ENST00000370018.7	TSL:1	c.1953C>T	p.Arg651Arg	synonymous	Exon 23 of 35	ENSP00000359035.3	Q9NZ71-1

Frequencies

GnomAD3 genomes AF: 0.00528 AC: 803 AN: 152172 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0971

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.0113 AC: 2804 AN: 248288 AF XY: 0.00953

Gnomad AFR exome AF: 0.00138

Gnomad AMR exome AF: 0.0245

Gnomad ASJ exome AF: 0.000606

Gnomad EAS exome AF: 0.0946

Gnomad FIN exome AF: 0.00145

Gnomad NFE exome AF: 0.000636

Gnomad OTH exome AF: 0.00711

GnomAD4 exome AF: 0.00405 AC: 5913 AN: 1460000 Hom.: 228 Cov.: 32 AF XY: 0.00382 AC XY: 2777 AN XY: 726268

African (AFR) AF: 0.000836 AC: 28 AN: 33478

American (AMR) AF: 0.0217 AC: 971 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.000498 AC: 13 AN: 26088

East Asian (EAS) AF: 0.0979 AC: 3885 AN: 39690

South Asian (SAS) AF: 0.00178 AC: 153 AN: 86186

European-Finnish (FIN) AF: 0.00121 AC: 63 AN: 52070

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5766

European-Non Finnish (NFE) AF: 0.000349 AC: 388 AN: 1111726

Other (OTH) AF: 0.00653 AC: 394 AN: 60336

GnomAD4 genome AF: 0.00530 AC: 807 AN: 152290 Hom.: 27 Cov.: 33 AF XY: 0.00571 AC XY: 425 AN XY: 74448

African (AFR) AF: 0.00140 AC: 58 AN: 41564

American (AMR) AF: 0.0105 AC: 160 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.0973 AC: 503 AN: 5168

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4828

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68018

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.00188 Hom.: 3

Bravo AF: 0.00679

Asia WGS AF: 0.0350 AC: 120 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000297

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Dyskeratosis congenita (1)
-	-	1	Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.2
DANN	Benign	0.95
PhyloP100		-0.057
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs79210260; hg19: chr20-62320929; COSMIC: COSV58894581; COSMIC: COSV58894581;