rs6011002

Positions:

• chr20-63666449-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001283009.2(RTEL1):​c.614+370A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 152,314 control chromosomes in the GnomAD database, including 615 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.085 (615 hom., cov: 33)
• Consequence: RTEL1 NM_001283009.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTEL1	NM_001283009.2	c.614+370A>G		intron_variant		ENST00000360203.11	NP_001269938.1
RTEL1-TNFRSF6B	NR_037882.1	n.1441+370A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTEL1	ENST00000360203.11	c.614+370A>G		intron_variant		5	NM_001283009.2	ENSP00000353332	A2

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12931 AN: 152196 Hom.: 611 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.0656

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0859

Gnomad OTH AF: 0.0722

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0850 AC: 12944 AN: 152314 Hom.: 615 Cov.: 33 AF XY: 0.0839 AC XY: 6247 AN XY: 74488

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0695

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0460

Gnomad4 FIN AF: 0.0656

Gnomad4 NFE AF: 0.0859

Gnomad4 OTH AF: 0.0719

Alfa AF: 0.0820 Hom.: 721

Bravo AF: 0.0847

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.43

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: rs6011002; hg19: chr20-62297802;