rs4809324

Positions:

• chr20-63686867-T-C

Variant summary

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

The NM_001283009.2(RTEL1):​c.1349-771T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 166,520 control chromosomes in the GnomAD database, including 994 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 0.091 (914 hom., cov: 33)
  • Exomes 𝑓: 0.10 (80 hom.)
• Consequence: RTEL1 NM_001283009.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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-TNFRSF6B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTEL1	NM_001283009.2	c.1349-771T>C		intron_variant		ENST00000360203.11	NP_001269938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTEL1	ENST00000360203.11	c.1349-771T>C		intron_variant		5	NM_001283009.2	ENSP00000353332.5
RTEL1	ENST00000508582.7	c.1421-771T>C		intron_variant		2		ENSP00000424307.2
RTEL1	ENST00000370018.7	c.1349-771T>C		intron_variant		1		ENSP00000359035.3
RTEL1-TNFRSF6B	ENST00000492259.6	n.1433-771T>C		intron_variant		5		ENSP00000457428.1

Frequencies

GnomAD3 genomes AF: 0.0908 AC: 13800 AN: 151974 Hom.: 904 Cov.: 33

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.101 AC: 1451 AN: 14428 Hom.: 80 Cov.: 0 AF XY: 0.0999 AC XY: 761 AN XY: 7616

Gnomad4 AFR exome AF: 0.0191

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.0547

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.0847

Gnomad4 FIN exome AF: 0.0640

Gnomad4 NFE exome AF: 0.0977

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.0909 AC: 13828 AN: 152092 Hom.: 914 Cov.: 33 AF XY: 0.0900 AC XY: 6695 AN XY: 74368

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.0591

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0583

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.113

Alfa AF: 0.109 Hom.: 1862

Bravo AF: 0.102

Asia WGS AF: 0.129 AC: 448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.65

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: rs4809324; hg19: chr20-62318220;