rs2297441

chr20-63696229-G-Achr20-63696229-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001283009.2(RTEL1):c.*371G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 316,230 control chromosomes in the GnomAD database, including 97,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.80 (50347 hom., cov: 33)
  • Exomes 𝑓: 0.74 (46829 hom.)
• Consequence: RTEL1 NM_001283009.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-63696229-G-A is Benign according to our data. Variant chr20-63696229-G-A is described in Lovd as [Benign].
• 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	UniProt
RTEL1	NM_001283009.2	c.*371G>A		3_prime_UTR_variant	35/35	ENST00000360203.11
RTEL1-TNFRSF6B	NR_037882.1	n.4726+375G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTEL1	ENST00000360203.11	c.*371G>A		3_prime_UTR_variant	35/35	5	NM_001283009.2	A2

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122365 AN: 152056 Hom.: 50291 Cov.: 33

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.805

GnomAD4 exome AF: 0.744 AC: 122059 AN: 164056 Hom.: 46829 Cov.: 0 AF XY: 0.744 AC XY: 62394 AN XY: 83880

Gnomad4 AFR exome AF: 0.940

Gnomad4 AMR exome AF: 0.771

Gnomad4 ASJ exome AF: 0.776

Gnomad4 EAS exome AF: 0.363

Gnomad4 SAS exome AF: 0.735

Gnomad4 FIN exome AF: 0.798

Gnomad4 NFE exome AF: 0.769

Gnomad4 OTH exome AF: 0.767

GnomAD4 genome AF: 0.805 AC: 122483 AN: 152174 Hom.: 50347 Cov.: 33 AF XY: 0.802 AC XY: 59675 AN XY: 74394

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.769

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.802

Alfa AF: 0.797 Hom.: 12212

Bravo AF: 0.807

Asia WGS AF: 0.591 AC: 2057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.8
Dann	Benign	0.82

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: rs2297441; hg19: chr20-62327582;