Variant chr20-63659310-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001283009.2(RTEL1):c.-93C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 835,946 control chromosomes in the GnomAD database, including 128,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24680 hom., cov: 33)

Exomes 𝑓: 0.54 ( 103867 hom. )

Consequence

RTEL1
NM_001283009.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.156

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:):

RTEL1-TNFRSF6B links:

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 20-63659310-C-T is Benign according to our data. Variant chr20-63659310-C-T is described in ClinVar as [Benign]. Clinvar id is 1260129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63659310-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTEL1	NM_001283009.2 linkuse as main transcript	c.-93C>T		5_prime_UTR_variant	2/35	ENST00000360203.11	NP_001269938.1
RTEL1-TNFRSF6B	NR_037882.1 linkuse as main transcript	n.735C>T		non_coding_transcript_exon_variant	2/38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTEL1	ENST00000360203.11 linkuse as main transcript	c.-93C>T		5_prime_UTR_variant	2/35	5	NM_001283009.2	ENSP00000353332	A2	Q9NZ71-6

Frequencies

GnomAD3 genomes

AF:

0.561

AC:

85327

AN:

151972

Hom.:

24663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.645

Gnomad AMR

AF:

0.518

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.674

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.582

Gnomad OTH

AF:

0.549

GnomAD4 exome

AF:

0.537

AC:

367385

AN:

683856

Hom.:

103867

Cov.:

AF XY:

0.533

AC XY:

193787

AN XY:

363618

show subpopulations

Gnomad4 AFR exome

AF:

0.581

Gnomad4 AMR exome

AF:

0.439

Gnomad4 ASJ exome

AF:

0.583

Gnomad4 EAS exome

AF:

0.123

Gnomad4 SAS exome

AF:

0.394

Gnomad4 FIN exome

AF:

0.662

Gnomad4 NFE exome

AF:

0.583

Gnomad4 OTH exome

AF:

0.541

GnomAD4 genome

AF:

0.561

AC:

85385

AN:

152090

Hom.:

24680

Cov.:

AF XY:

0.561

AC XY:

41685

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.589

Gnomad4 AMR

AF:

0.517

Gnomad4 ASJ

AF:

0.580

Gnomad4 EAS

AF:

0.135

Gnomad4 SAS

AF:

0.370

Gnomad4 FIN

AF:

0.674

Gnomad4 NFE

AF:

0.582

Gnomad4 OTH

AF:

0.544

Alfa

AF:

0.553

Hom.:

6709

Bravo

AF:

0.550

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 68% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.1

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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