rs2242652

chr5-1279913-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198253.3(TERT):c.1950+245C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,150 control chromosomes in the GnomAD database, including 2,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.18 (2398 hom., cov: 33)
• Consequence: TERT NM_198253.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.61

Genes affected

TERT (HGNC:11730): (telomerase reverse transcriptase) Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component which serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells resulting in progressive shortening of telomeres. Deregulation of telomerase expression in somatic cells may be involved in oncogenesis. Studies in mouse suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. Alternatively spliced variants encoding different isoforms of telomerase reverse transcriptase have been identified; the full-length sequence of some variants has not been determined. Alternative splicing at this locus is thought to be one mechanism of regulation of telomerase activity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 5-1279913-G-A is Benign according to our data. Variant chr5-1279913-G-A is described in ClinVar as [Benign]. Clinvar id is 539266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERT	NM_198253.3	c.1950+245C>T		intron_variant		ENST00000310581.10
TERT	NM_001193376.3	c.1950+245C>T		intron_variant
TERT	NR_149162.3	n.2029+245C>T		intron_variant, non_coding_transcript_variant
TERT	NR_149163.3	n.2029+245C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERT	ENST00000310581.10	c.1950+245C>T		intron_variant		1	NM_198253.3	P2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26806 AN: 152032 Hom.: 2399 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.176 AC: 26800 AN: 152150 Hom.: 2398 Cov.: 33 AF XY: 0.176 AC XY: 13112 AN XY: 74386

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.205

Alfa AF: 0.183 Hom.: 968

Bravo AF: 0.169

Asia WGS AF: 0.183 AC: 640 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 24, 2018

This variant is associated with the following publications: (PMID: 23535731) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.80
Dann	Benign	0.62

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: rs2242652; hg19: chr5-1280028; COSMIC: COSV57205318;