rs6089953

Positions:

• chr20-63659655-A-G
• chr20-63659655-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001283009.2(RTEL1):​c.102+151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 661,582 control chromosomes in the GnomAD database, including 199,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (51200 hom., cov: 33)
  • Exomes 𝑓: 0.75 (148605 hom.)
• Consequence: RTEL1 NM_001283009.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0260

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 20-63659655-A-G is Benign according to our data. Variant chr20-63659655-A-G is described in ClinVar as [Benign]. Clinvar id is 1291608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTEL1	NM_001283009.2	c.102+151A>G		intron_variant		ENST00000360203.11
RTEL1-TNFRSF6B	NR_037882.1	n.929+151A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTEL1	ENST00000360203.11	c.102+151A>G		intron_variant		5	NM_001283009.2	A2

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123271 AN: 152094 Hom.: 51139 Cov.: 33

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.806

GnomAD4 exome AF: 0.753 AC: 383400 AN: 509370 Hom.: 148605 AF XY: 0.752 AC XY: 203571 AN XY: 270638

Gnomad4 AFR exome AF: 0.943

Gnomad4 AMR exome AF: 0.830

Gnomad4 ASJ exome AF: 0.777

Gnomad4 EAS exome AF: 0.301

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.806

Gnomad4 NFE exome AF: 0.775

Gnomad4 OTH exome AF: 0.761

GnomAD4 genome AF: 0.811 AC: 123397 AN: 152212 Hom.: 51200 Cov.: 33 AF XY: 0.808 AC XY: 60123 AN XY: 74402

Gnomad4 AFR AF: 0.939

Gnomad4 AMR AF: 0.832

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.804

Alfa AF: 0.789 Hom.: 27914

Bravo AF: 0.816

Asia WGS AF: 0.563 AC: 1959 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.37

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

Other links and lift over

dbSNP: rs6089953; hg19: chr20-62291008;