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GeneBe

rs2736100

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_198253.3(TERT):c.1574-3777G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,908 control chromosomes in the GnomAD database, including 20,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.52 ( 20520 hom., cov: 31)

Consequence

TERT
NM_198253.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter U:1B:1O:3

Conservation

PhyloP100: -1.13
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.01).
BP6
Variant 5-1286401-C-A is Benign according to our data. Variant chr5-1286401-C-A is described in ClinVar as [Benign]. Clinvar id is 375480.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TERTNM_198253.3 linkuse as main transcriptc.1574-3777G>T intron_variant ENST00000310581.10
TERTNM_001193376.3 linkuse as main transcriptc.1574-3777G>T intron_variant
TERTNR_149162.3 linkuse as main transcriptn.1653-3777G>T intron_variant, non_coding_transcript_variant
TERTNR_149163.3 linkuse as main transcriptn.1653-3777G>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TERTENST00000310581.10 linkuse as main transcriptc.1574-3777G>T intron_variant 1 NM_198253.3 P2O14746-1
TERTENST00000334602.10 linkuse as main transcriptc.1574-3777G>T intron_variant 1 A2O14746-3
TERTENST00000460137.6 linkuse as main transcriptc.1574-3777G>T intron_variant, NMD_transcript_variant 1 O14746-4
TERTENST00000656021.1 linkuse as main transcriptc.*883G>T 3_prime_UTR_variant, NMD_transcript_variant 3/17

Frequencies

GnomAD3 genomes
AF:
0.519
AC:
78709
AN:
151790
Hom.:
20496
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.539
Gnomad AMI
AF:
0.469
Gnomad AMR
AF:
0.597
Gnomad ASJ
AF:
0.447
Gnomad EAS
AF:
0.588
Gnomad SAS
AF:
0.411
Gnomad FIN
AF:
0.520
Gnomad MID
AF:
0.311
Gnomad NFE
AF:
0.497
Gnomad OTH
AF:
0.497
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.519
AC:
78771
AN:
151908
Hom.:
20520
Cov.:
31
AF XY:
0.521
AC XY:
38654
AN XY:
74238
show subpopulations
Gnomad4 AFR
AF:
0.539
Gnomad4 AMR
AF:
0.597
Gnomad4 ASJ
AF:
0.447
Gnomad4 EAS
AF:
0.588
Gnomad4 SAS
AF:
0.411
Gnomad4 FIN
AF:
0.520
Gnomad4 NFE
AF:
0.497
Gnomad4 OTH
AF:
0.492
Alfa
AF:
0.494
Hom.:
34252
Bravo
AF:
0.528
Asia WGS
AF:
0.469
AC:
1632
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Uncertain:1Benign:1Other:3
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Chronic obstructive pulmonary disease Uncertain:1
Uncertain significance, no assertion criteria providedcase-controlHLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio VillegasMay 04, 2021- -
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
Interstitial lung disease 2 Other:1
association, no assertion criteria providedcase-controlHLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio VillegasMay 04, 2021- -
Chronic osteomyelitis Other:1
association, no assertion criteria providedcase-controlDepartment of Orthopeadics and Traumatology, Nanfang HospitalSep 01, 2016- -
Combined pulmonary fibrosis-emphysema syndrome Other:1
association, no assertion criteria providedcase-controlHLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio VillegasMay 04, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
Cadd
Benign
0.050
Dann
Benign
0.33

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2736100; hg19: chr5-1286516; COSMIC: COSV57244861; COSMIC: COSV57244861; API