20-63659344-A-C

Variant names:

• chr20-63659344-A-C
• rs13043797
• NM_001283009.2:c.-59A>C

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.-59A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 1,320,270 control chromosomes in the GnomAD database, including 2,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (172 hom., cov: 33)
  • Exomes 𝑓: 0.056 (2197 hom.)
• Consequence: RTEL1 NM_001283009.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.119
• Publications: 12 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=-0.82).
• BP6: Variant 20-63659344-A-C is Benign according to our data. Variant chr20-63659344-A-C is described in ClinVar as Benign. ClinVar VariationId is 1279544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0606 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001283009.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTEL1	NM_001283009.2	MANE Select	c.-59A>C		5_prime_UTR	Exon 2 of 35	NP_001269938.1	Q9NZ71-6
	RTEL1	NM_032957.5		c.-59A>C		5_prime_UTR	Exon 2 of 35	NP_116575.3	Q9NZ71-7
	RTEL1	NM_016434.4		c.-59A>C		5_prime_UTR	Exon 2 of 35	NP_057518.1	Q9NZ71-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTEL1	ENST00000360203.11	TSL:5 MANE Select	c.-59A>C		5_prime_UTR	Exon 2 of 35	ENSP00000353332.5	Q9NZ71-6
	RTEL1	ENST00000508582.7	TSL:2	c.-59A>C		5_prime_UTR	Exon 2 of 35	ENSP00000424307.2	Q9NZ71-7
	RTEL1	ENST00000370018.7	TSL:1	c.-59A>C		5_prime_UTR	Exon 2 of 35	ENSP00000359035.3	Q9NZ71-1

Frequencies

GnomAD3 genomes AF: 0.0386 AC: 5873 AN: 152122 Hom.: 172 Cov.: 33

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0174

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.0596

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0622

Gnomad OTH AF: 0.0298

GnomAD4 exome AF: 0.0557 AC: 65023 AN: 1168030 Hom.: 2197 Cov.: 16 AF XY: 0.0537 AC XY: 31875 AN XY: 593646

African (AFR) AF: 0.00875 AC: 242 AN: 27664

American (AMR) AF: 0.0143 AC: 619 AN: 43360

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 516 AN: 24218

East Asian (EAS) AF: 0.000261 AC: 10 AN: 38268

South Asian (SAS) AF: 0.00952 AC: 757 AN: 79490

European-Finnish (FIN) AF: 0.0579 AC: 3070 AN: 53016

Middle Eastern (MID) AF: 0.00312 AC: 15 AN: 4806

European-Non Finnish (NFE) AF: 0.0679 AC: 57434 AN: 846480

Other (OTH) AF: 0.0465 AC: 2360 AN: 50728

GnomAD4 genome AF: 0.0386 AC: 5870 AN: 152240 Hom.: 172 Cov.: 33 AF XY: 0.0369 AC XY: 2748 AN XY: 74424

African (AFR) AF: 0.0110 AC: 458 AN: 41548

American (AMR) AF: 0.0173 AC: 265 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 84 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.00830 AC: 40 AN: 4822

European-Finnish (FIN) AF: 0.0596 AC: 632 AN: 10596

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0622 AC: 4230 AN: 68006

Other (OTH) AF: 0.0295 AC: 62 AN: 2104

Alfa AF: 0.0530 Hom.: 194

Bravo AF: 0.0346

Asia WGS AF: 0.00953 AC: 34 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.58
PhyloP100		0.12
Mutation Taster		=300/0	polymorphism

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: rs13043797; hg19: chr20-62290697; COSMIC: COSV58892799; COSMIC: COSV58892799;