5-1282204-C-A

Position:

• chr5-1282204-C-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.1769+225G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,134 control chromosomes in the GnomAD database, including 6,964 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.30 (6964 hom., cov: 33)
• Consequence: TERT NM_198253.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.377

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]

TERT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-1282204-C-A is Benign according to our data. Variant chr5-1282204-C-A is described in ClinVar as [Benign]. Clinvar id is 225784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERT	NM_198253.3	c.1769+225G>T		intron_variant		ENST00000310581.10	NP_937983.2
TERT	NM_001193376.3	c.1769+225G>T		intron_variant			NP_001180305.1
TERT	NR_149162.3	n.1848+225G>T		intron_variant
TERT	NR_149163.3	n.1848+225G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TERT	ENST00000310581.10	c.1769+225G>T		intron_variant		1	NM_198253.3	ENSP00000309572.5

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45015 AN: 152016 Hom.: 6960 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.296 AC: 45027 AN: 152134 Hom.: 6964 Cov.: 33 AF XY: 0.295 AC XY: 21909 AN XY: 74342

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.364

Alfa AF: 0.310 Hom.: 1648

Bravo AF: 0.289

Asia WGS AF: 0.432 AC: 1501 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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 14, 2018

This variant is associated with the following publications: (PMID: 30680798) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.80
DANN	Benign	0.58

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: rs7726159; hg19: chr5-1282319; COSMIC: COSV104394523;