rs2853677

Positions:

• chr5-1287079-G-A
• chr5-1287079-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198253.3(TERT):​c.1574-4455C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,954 control chromosomes in the GnomAD database, including 30,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.63 (30173 hom., cov: 31)
• Consequence: TERT NM_198253.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.614

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 5-1287079-G-A is Benign according to our data. Variant chr5-1287079-G-A is described in ClinVar as [Benign]. Clinvar id is 1167534.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERT	NM_198253.3	c.1574-4455C>T		intron_variant		ENST00000310581.10	NP_937983.2
TERT	NM_001193376.3	c.1574-4455C>T		intron_variant			NP_001180305.1
TERT	NR_149162.3	n.1653-4455C>T		intron_variant
TERT	NR_149163.3	n.1653-4455C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TERT	ENST00000310581.10	c.1574-4455C>T		intron_variant		1	NM_198253.3	ENSP00000309572.5

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94938 AN: 151838 Hom.: 30129 Cov.: 31

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.625 AC: 95029 AN: 151954 Hom.: 30173 Cov.: 31 AF XY: 0.625 AC XY: 46437 AN XY: 74244

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.555

Alfa AF: 0.578 Hom.: 31568

Bravo AF: 0.637

Asia WGS AF: 0.514 AC: 1791 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.60

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: rs2853677; hg19: chr5-1287194;