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rs10069690

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198253.3(TERT):c.1951-205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,058 control chromosomes in the GnomAD database, including 10,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10955 hom., cov: 33)

Consequence

TERT
NM_198253.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -1.93
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.02).
BP6
Variant 5-1279675-C-T is Benign according to our data. Variant chr5-1279675-C-T is described in ClinVar as [Benign]. Clinvar id is 225783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TERTNM_198253.3 linkuse as main transcriptc.1951-205G>A intron_variant ENST00000310581.10
TERTNM_001193376.3 linkuse as main transcriptc.1951-205G>A intron_variant
TERTNR_149162.3 linkuse as main transcriptn.2030-205G>A intron_variant, non_coding_transcript_variant
TERTNR_149163.3 linkuse as main transcriptn.2030-205G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TERTENST00000310581.10 linkuse as main transcriptc.1951-205G>A intron_variant 1 NM_198253.3 P2O14746-1

Frequencies

GnomAD3 genomes
AF:
0.349
AC:
53038
AN:
151940
Hom.:
10937
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.590
Gnomad AMI
AF:
0.277
Gnomad AMR
AF:
0.234
Gnomad ASJ
AF:
0.322
Gnomad EAS
AF:
0.179
Gnomad SAS
AF:
0.258
Gnomad FIN
AF:
0.296
Gnomad MID
AF:
0.323
Gnomad NFE
AF:
0.259
Gnomad OTH
AF:
0.337
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.349
AC:
53094
AN:
152058
Hom.:
10955
Cov.:
33
AF XY:
0.346
AC XY:
25703
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.590
Gnomad4 AMR
AF:
0.233
Gnomad4 ASJ
AF:
0.322
Gnomad4 EAS
AF:
0.178
Gnomad4 SAS
AF:
0.256
Gnomad4 FIN
AF:
0.296
Gnomad4 NFE
AF:
0.259
Gnomad4 OTH
AF:
0.335
Alfa
AF:
0.275
Hom.:
8912
Bravo
AF:
0.353
Asia WGS
AF:
0.257
AC:
899
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxOct 24, 2018This variant is associated with the following publications: (PMID: 26143636, 25919761, 26053551, 23535731, 22037553, 23066086) -
Chronic osteomyelitis Other:1
association, no assertion criteria providedcase-controlDepartment of Orthopeadics and Traumatology, Nanfang HospitalSep 01, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
Cadd
Benign
7.8
Dann
Benign
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.24
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.24
Position offset: 3

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: rs10069690; hg19: chr5-1279790; API