20-63678486-A-G

Position:

• chr20-63678486-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001283009.2(RTEL1):​c.1037+140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 728,936 control chromosomes in the GnomAD database, including 213,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.80 (49924 hom., cov: 30)
  • Exomes 𝑓: 0.74 (163625 hom.)
• Consequence: RTEL1 NM_001283009.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.45

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 20-63678486-A-G is Benign according to our data. Variant chr20-63678486-A-G is described in ClinVar as [Benign]. Clinvar id is 1259728.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTEL1	NM_001283009.2	c.1037+140A>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.1037+140A>G		intron_variant		5	NM_001283009.2	ENSP00000353332.5
RTEL1	ENST00000508582.7	c.1109+140A>G		intron_variant		2		ENSP00000424307.2
RTEL1	ENST00000370018.7	c.1037+140A>G		intron_variant		1		ENSP00000359035.3
RTEL1-TNFRSF6B	ENST00000492259.6	n.1121+140A>G		intron_variant		5		ENSP00000457428.1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121584 AN: 151900 Hom.: 49863 Cov.: 30

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.793

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.791

GnomAD4 exome AF: 0.742 AC: 428360 AN: 576918 Hom.: 163625 AF XY: 0.743 AC XY: 222379 AN XY: 299498

Gnomad4 AFR exome AF: 0.943

Gnomad4 AMR exome AF: 0.721

Gnomad4 ASJ exome AF: 0.755

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.731

Gnomad4 FIN exome AF: 0.807

Gnomad4 NFE exome AF: 0.768

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.801 AC: 121708 AN: 152018 Hom.: 49924 Cov.: 30 AF XY: 0.797 AC XY: 59201 AN XY: 74294

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.800

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.789

Alfa AF: 0.761 Hom.: 97335

Bravo AF: 0.799

Asia WGS AF: 0.547 AC: 1905 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.98
CADD	Benign	1.3
DANN	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6010620; hg19: chr20-62309839;