rs2297440

Positions:

• chr20-63680946-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001283009.2(RTEL1):​c.1191+227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 985,136 control chromosomes in the GnomAD database, including 292,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (50346 hom., cov: 32)
  • Exomes 𝑓: 0.76 (241915 hom.)
• Consequence: RTEL1 NM_001283009.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.362

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-63680946-T-C is Benign according to our data. Variant chr20-63680946-T-C is described in ClinVar as [Benign]. Clinvar id is 1224071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTEL1	NM_001283009.2	c.1191+227T>C		intron_variant		ENST00000360203.11
RTEL1-TNFRSF6B	NR_037882.1	n.2018+227T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTEL1	ENST00000360203.11	c.1191+227T>C		intron_variant		5	NM_001283009.2	A2

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122164 AN: 151996 Hom.: 50285 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.796

GnomAD4 exome AF: 0.760 AC: 633479 AN: 833022 Hom.: 241915 Cov.: 39 AF XY: 0.761 AC XY: 292584 AN XY: 384682

Gnomad4 AFR exome AF: 0.957

Gnomad4 AMR exome AF: 0.700

Gnomad4 ASJ exome AF: 0.753

Gnomad4 EAS exome AF: 0.276

Gnomad4 SAS exome AF: 0.746

Gnomad4 FIN exome AF: 0.775

Gnomad4 NFE exome AF: 0.760

Gnomad4 OTH exome AF: 0.738

GnomAD4 genome AF: 0.804 AC: 122288 AN: 152114 Hom.: 50346 Cov.: 32 AF XY: 0.800 AC XY: 59494 AN XY: 74346

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.771

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.729

Gnomad4 FIN AF: 0.800

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.794

Alfa AF: 0.783 Hom.: 24608

Bravo AF: 0.804

Asia WGS AF: 0.550 AC: 1916 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs2297440; hg19: chr20-62312299;