rs140738232

chr20-63689084-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001283009.2(RTEL1):c.1830C>T(p.Ala610=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000832 in 1,610,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: RTEL1 NM_001283009.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.678

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 20-63689084-C-T is Benign according to our data. Variant chr20-63689084-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 540946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.678 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTEL1	NM_001283009.2	c.1830C>T	p.Ala610=	synonymous_variant	22/35	ENST00000360203.11
RTEL1-TNFRSF6B	NR_037882.1	n.2657C>T		non_coding_transcript_exon_variant	22/38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTEL1	ENST00000360203.11	c.1830C>T	p.Ala610=	synonymous_variant	22/35	5	NM_001283009.2	A2

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152140 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000169 AC: 42 AN: 248454 Hom.: 0 AF XY: 0.000163 AC XY: 22 AN XY: 134982

Gnomad AFR exome AF: 0.0000622

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00260

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000445

Gnomad OTH exome AF: 0.000493

GnomAD4 exome AF: 0.0000754 AC: 110 AN: 1458690 Hom.: 0 Cov.: 32 AF XY: 0.0000703 AC XY: 51 AN XY: 725762

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00279

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.000199

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152140 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15 AN XY: 74312

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000479

Alfa AF: 0.000273 Hom.: 0

Bravo AF: 0.000140

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Dyskeratosis congenita Benign:1

Likely benign, criteria provided, single submitter

curation

Sema4, Sema4

Jan 26, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	2.2
Dann	Benign	0.70
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1

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: rs140738232; hg19: chr20-62320437;