20-63677259-T-G

Variant names:

• chr20-63677259-T-G
• rs2738783
• NM_001283009.2:c.920-886T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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 -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.

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.920-886T>G		intron	N/A	NP_001269938.1	Q9NZ71-6
	RTEL1	NM_032957.5		c.992-886T>G		intron	N/A	NP_116575.3	Q9NZ71-7
	RTEL1	NM_016434.4		c.920-886T>G		intron	N/A	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.920-886T>G		intron	N/A	ENSP00000353332.5	Q9NZ71-6
	RTEL1	ENST00000508582.7	TSL:2	c.992-886T>G		intron	N/A	ENSP00000424307.2	Q9NZ71-7
	RTEL1	ENST00000370018.7	TSL:1	c.920-886T>G		intron	N/A	ENSP00000359035.3	Q9NZ71-1

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

African (AFR) AF: 0.948 AC: 39365 AN: 41526

American (AMR) AF: 0.802 AC: 12260 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2878 AN: 3472

East Asian (EAS) AF: 0.589 AC: 3047 AN: 5172

South Asian (SAS) AF: 0.768 AC: 3710 AN: 4830

European-Finnish (FIN) AF: 0.832 AC: 8812 AN: 10590

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.809 AC: 55022 AN: 68020

Other (OTH) AF: 0.836 AC: 1767 AN: 2114

Alfa AF: 0.808 Hom.: 26494

Bravo AF: 0.841

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.49
PhyloP100		0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2738783; hg19: chr20-62308612;