NM_001283009.2:c.102+151A>G

Variant names:

• chr20-63659655-A-G
• rs6089953
• NM_001283009.2:c.102+151A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001283009.2(RTEL1):​c.102+151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 661,582 control chromosomes in the GnomAD database, including 199,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (51200 hom., cov: 33)
  • Exomes 𝑓: 0.75 (148605 hom.)
• Consequence: RTEL1 NM_001283009.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0260
• Publications: 37 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 20-63659655-A-G is Benign according to our data. Variant chr20-63659655-A-G is described in ClinVar as Benign. ClinVar VariationId is 1291608.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 rank	MANE	Protein	UniProt
RTEL1	NM_001283009.2	c.102+151A>G		intron_variant	Intron 2 of 34	ENST00000360203.11	NP_001269938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTEL1	ENST00000360203.11	c.102+151A>G		intron_variant	Intron 2 of 34	5	NM_001283009.2	ENSP00000353332.5
RTEL1	ENST00000508582.7	c.102+151A>G		intron_variant	Intron 2 of 34	2		ENSP00000424307.2
RTEL1	ENST00000370018.7	c.102+151A>G		intron_variant	Intron 2 of 34	1		ENSP00000359035.3
RTEL1-TNFRSF6B	ENST00000492259.6	n.102+151A>G		intron_variant	Intron 1 of 34	5		ENSP00000457428.1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123271 AN: 152094 Hom.: 51139 Cov.: 33

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.806

GnomAD4 exome AF: 0.753 AC: 383400 AN: 509370 Hom.: 148605 AF XY: 0.752 AC XY: 203571 AN XY: 270638

African (AFR) AF: 0.943 AC: 13497 AN: 14320

American (AMR) AF: 0.830 AC: 23109 AN: 27832

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 12445 AN: 16010

East Asian (EAS) AF: 0.301 AC: 9481 AN: 31522

South Asian (SAS) AF: 0.750 AC: 40567 AN: 54114

European-Finnish (FIN) AF: 0.806 AC: 30091 AN: 37314

Middle Eastern (MID) AF: 0.799 AC: 3052 AN: 3822

European-Non Finnish (NFE) AF: 0.775 AC: 229583 AN: 296090

Other (OTH) AF: 0.761 AC: 21575 AN: 28346

GnomAD4 genome AF: 0.811 AC: 123397 AN: 152212 Hom.: 51200 Cov.: 33 AF XY: 0.808 AC XY: 60123 AN XY: 74402

African (AFR) AF: 0.939 AC: 39011 AN: 41562

American (AMR) AF: 0.832 AC: 12698 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2690 AN: 3472

East Asian (EAS) AF: 0.297 AC: 1536 AN: 5174

South Asian (SAS) AF: 0.740 AC: 3566 AN: 4822

European-Finnish (FIN) AF: 0.801 AC: 8483 AN: 10592

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52724 AN: 68004

Other (OTH) AF: 0.804 AC: 1698 AN: 2112

Alfa AF: 0.783 Hom.: 39054

Bravo AF: 0.816

Asia WGS AF: 0.563 AC: 1959 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.37
PhyloP100		-0.026
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6089953; hg19: chr20-62291008; COSMIC: COSV107378207; COSMIC: COSV107378207;