5-1266195-A-G

Position:

• chr5-1266195-A-G

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.2654+269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,090 control chromosomes in the GnomAD database, including 23,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.54 (23749 hom., cov: 33)
• Consequence: TERT NM_198253.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.74

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=-1.04).
• BP6: Variant 5-1266195-A-G is Benign according to our data. Variant chr5-1266195-A-G is described in ClinVar as [Benign]. Clinvar id is 539247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERT	NM_198253.3	c.2654+269T>C		intron_variant		ENST00000310581.10	NP_937983.2
TERT	NM_001193376.3	c.2654+269T>C		intron_variant			NP_001180305.1
TERT	NR_149162.3	n.2551+269T>C		intron_variant
TERT	NR_149163.3	n.2515+269T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TERT	ENST00000310581.10	c.2654+269T>C		intron_variant		1	NM_198253.3	ENSP00000309572.5

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82848 AN: 151972 Hom.: 23754 Cov.: 33

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.545 AC: 82867 AN: 152090 Hom.: 23749 Cov.: 33 AF XY: 0.535 AC XY: 39783 AN XY: 74356

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.574

Alfa AF: 0.636 Hom.: 21129

Bravo AF: 0.534

Asia WGS AF: 0.350 AC: 1221 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: 22948024) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.082
DANN	Benign	0.084

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2075786; hg19: chr5-1266310;