20-63677259-T-G

Position:

• chr20-63677259-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001283009.2(RTEL1):​c.920-886T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 152,220 control chromosomes in the GnomAD database, including 54,250 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (54250 hom., cov: 33)
• Consequence: RTEL1 NM_001283009.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

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]

RTEL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTEL1	NM_001283009.2	c.920-886T>G		intron_variant		ENST00000360203.11	NP_001269938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTEL1	ENST00000360203.11	c.920-886T>G		intron_variant		5	NM_001283009.2	ENSP00000353332.5
RTEL1	ENST00000508582.7	c.992-886T>G		intron_variant		2		ENSP00000424307.2
RTEL1	ENST00000370018.7	c.920-886T>G		intron_variant		1		ENSP00000359035.3
RTEL1-TNFRSF6B	ENST00000492259.6	n.920-886T>G		intron_variant		5		ENSP00000457428.1

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127740 AN: 152102 Hom.: 54190 Cov.: 33

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.837

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.840 AC: 127859 AN: 152220 Hom.: 54250 Cov.: 33 AF XY: 0.838 AC XY: 62357 AN XY: 74428

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.809

Gnomad4 OTH AF: 0.836

Alfa AF: 0.810 Hom.: 8543

Bravo AF: 0.841

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2738783; hg19: chr20-62308612;