rs116900568

Variant names:

• chr20-63688566-G-A
• rs116900568
• NM_001283009.2:c.1761G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-63688566-G-A
• chr20-63688566-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001283009.2(RTEL1):​c.1761G>A​(p.Pro587Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,610,322 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P587P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0033 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (28 hom.)
• Consequence: RTEL1 NM_001283009.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -3.93
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 20-63688566-G-A is Benign according to our data. Variant chr20-63688566-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 436567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.93 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00333 (507/152334) while in subpopulation AMR AF = 0.00438 (67/15312). AF 95% confidence interval is 0.00385. There are 3 homozygotes in GnomAd4. There are 230 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AD,SD,AR gene

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.1761G>A	p.Pro587Pro	synonymous	Exon 21 of 35	NP_001269938.1	Q9NZ71-6
	RTEL1	NM_032957.5		c.1833G>A	p.Pro611Pro	synonymous	Exon 21 of 35	NP_116575.3	Q9NZ71-7
	RTEL1	NM_016434.4		c.1761G>A	p.Pro587Pro	synonymous	Exon 21 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.1761G>A	p.Pro587Pro	synonymous	Exon 21 of 35	ENSP00000353332.5	Q9NZ71-6
	RTEL1	ENST00000508582.7	TSL:2	c.1833G>A	p.Pro611Pro	synonymous	Exon 21 of 35	ENSP00000424307.2	Q9NZ71-7
	RTEL1	ENST00000370018.7	TSL:1	c.1761G>A	p.Pro587Pro	synonymous	Exon 21 of 35	ENSP00000359035.3	Q9NZ71-1

Frequencies

GnomAD3 genomes AF: 0.00334 AC: 509 AN: 152216 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00372

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00426

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00367 AC: 895 AN: 244144 AF XY: 0.00382

Gnomad AFR exome AF: 0.000579

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.0211

Gnomad EAS exome AF: 0.0000549

Gnomad FIN exome AF: 0.000148

Gnomad NFE exome AF: 0.00439

Gnomad OTH exome AF: 0.00521

GnomAD4 exome AF: 0.00355 AC: 5183 AN: 1457988 Hom.: 28 Cov.: 33 AF XY: 0.00359 AC XY: 2603 AN XY: 725264

African (AFR) AF: 0.000717 AC: 24 AN: 33456

American (AMR) AF: 0.00290 AC: 129 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 533 AN: 26040

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39664

South Asian (SAS) AF: 0.00232 AC: 199 AN: 85892

European-Finnish (FIN) AF: 0.000233 AC: 12 AN: 51404

Middle Eastern (MID) AF: 0.0204 AC: 109 AN: 5346

European-Non Finnish (NFE) AF: 0.00350 AC: 3888 AN: 1111400

Other (OTH) AF: 0.00478 AC: 288 AN: 60262

GnomAD4 genome AF: 0.00333 AC: 507 AN: 152334 Hom.: 3 Cov.: 33 AF XY: 0.00309 AC XY: 230 AN XY: 74478

African (AFR) AF: 0.000770 AC: 32 AN: 41582

American (AMR) AF: 0.00438 AC: 67 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4830

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00425 AC: 289 AN: 68028

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00459 Hom.: 1

Bravo AF: 0.00309

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not provided (6)
-	-	2	not specified (2)
-	-	1	Dyskeratosis congenita (1)
-	-	1	Dyskeratosis congenita, autosomal recessive 5 (1)
-	-	1	Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.4
DANN	Benign	0.91
PhyloP100		-3.9
PromoterAI		-0.0052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs116900568; hg19: chr20-62319919;