About TERT
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
TERT c.1950+10C>T, p.?
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BA1Stand alone
BA1 · stand alone
Population frequency exceeds the generic BA1 threshold of 1%. This variant is present at 1.36750% in gnomAD v2.1 and 1.21665% in gnomAD v4.1, with the highest observed frequency in the Finnish population at about 4.14% and 4.07%, respectively, which strongly supports a benign interpretation.
BP4Supporting
BP4 · supporting
Available computational evidence supports no meaningful impact on splicing. SpliceAI predicts no significant splice effect, with a maximum delta score of 0.07, which is below commonly used thresholds for splice disruption.
Recorded classification: Benign
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BA1 stand-alone benign, BP4 supporting; combination = 1 stand-alone benign + 1 supporting benign, which maps to Benign.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
19,637 / 1,614,020 alleles
gnomAD v4.1: 19,637 / 1,614,020 alleles. Recorded AF 0.0121665. Recorded homozygote count 187.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.013675; MAF= 1.36750%, 3864/282560 alleles, homozygotes = 49) and has highest observed frequency in the European (Finnish) population (AF= 0.0414013; MAF= 4.14013%, 1040/25120 alleles, homozygotes = 22); grpmax FAF= 0.0239814.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0109168; MAF= 1.09168%, 201/18412 alleles, homozygotes = 1) and has highest observed frequency in the afr population (AF= 0.0205882; grpmax FAF95= 0.013796).
SpliceAI score
0.070 maximum delta
Recorded SpliceAI maximum delta score: 0.070. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
14 reported laboratory submissions
14 Benign.
Context only
ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
OncoKB ↗
Somatic evidence
8 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV57245267, n = 8 times).
Context only
COSMIC ↗
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 3 not met · 13 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The TERT c.1950+10C>T (p.?) variant has been reported in ClinVar as Benign by 14 clinical laboratories.
This variant is common in population databases, with allele frequencies of 1.36750% in gnomAD v2.1 and 1.21665% in gnomAD v4.1, both above the 1% BA1 threshold, and reaches approximately 4.14% to 4.07% in the Finnish population.
In silico splice prediction does not support a clinically meaningful splicing effect, with SpliceAI showing a maximum delta score of 0.07.
No criteria match.
Met · 2
BA1 Stand alonePopulation frequency exceeds the generic BA1 threshold of 1%. This variant is present at 1.36750% in gnomAD v2.1 and 1.21665% in gnomAD v4.1, with the highest observed frequency in the Finnish population at about 4.14% and 4.07%, respectively, which strongly supports a benign interpretation. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 total AF 0.013674971687429219
- Finnish AF 0.041401273885350316
- 49 homozygotes.
- gnomAD v4.1 total AF 0.012166515904387802
- Finnish AF 0.04074955383700178
- 187 homozygotes.
Sources
BP4 SupportingAvailable computational evidence supports no meaningful impact on splicing. SpliceAI predicts no significant splice effect, with a maximum delta score of 0.07, which is below commonly used thresholds for splice disruption. Details ▾Hide ▴
Not met · 3 · evaluated, threshold not reached
PS4 Available evidence does not show that this variant is enriched in affected individuals compared with controls. Details ▾Hide ▴
Evidence considered
- ClinVar shows benign clinical-laboratory submissions rather than case-enrichment evidence.
Still missing
- Case-control or statistically enriched affected-case data were not identified.
Sources
PM2 This variant is not absent from population databases; instead, it is common in gnomAD with total allele frequencies of 1.36750% in v2.1 and 1.21665% in v4.1, which is far above the generic PM2 rarity threshold of 0.1%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 total AF 0.013674971687429219 (3864/282560)
- Finnish AF 0.041401273885350316.
- gnomAD v4.1 total AF 0.012166515904387802 (19637/1614020)
- Finnish AF 0.04074955383700178.
Sources
PP3 Available computational evidence does not support a damaging effect on splicing. SpliceAI predicts no significant splice impact, with a maximum delta score of 0.07, which is below commonly used concern thresholds. Details ▾Hide ▴
Evidence considered
- SpliceAI DS_AG 0.00
- DS_AL 0.00
- DS_DG 0.05
- DS_DL 0.07
- max delta score 0.07.
Sources
Not assessed · 13 · no assessment recorded
PS2 No confirmed de novo data with verified parentage were identified for this variant. Details ▾Hide ▴
Still missing
- Documented trio-based de novo evidence was not identified.
PS3 No validated functional study of this exact variant showing a damaging effect was identified. Details ▾Hide ▴
Still missing
- Variant-specific functional or RNA evidence demonstrating a damaging effect was not identified.
PM3 No evidence was identified showing this variant in trans with a pathogenic variant in a recessive disease setting. Details ▾Hide ▴
Still missing
- Phase-confirmed trans observations were not identified.
PM6 No assumed de novo occurrence data were identified for this variant. Details ▾Hide ▴
Still missing
- De novo evidence without full parentage confirmation was not identified.
PP1 No segregation data were identified for this variant. Details ▾Hide ▴
Still missing
- Family segregation evidence was not identified.
PP4 No phenotype data specific enough to support a highly characteristic TERT-related presentation for this variant were identified. Details ▾Hide ▴
Still missing
- Phenotype specificity and case-level clinical correlation were not identified.
PP5 PP5 was not used because primary supporting evidence for a pathogenic classification was not identified, and this criterion is not relied on here. Details ▾Hide ▴
No further detail was recorded.
BS2 Although this variant is observed many times in population databases, no dataset-specific healthy adult phenotyping framework was identified to support independent BS2 application. Details ▾Hide ▴
Evidence considered
- The variant is present in population databases
- including homozygotes.
Still missing
- Phenotyped unaffected-adult evidence suitable for BS2 was not identified.
Sources
BS3 No validated functional study of this exact variant showing a normal or no-impact effect was identified. Details ▾Hide ▴
Still missing
- Variant-specific benign functional or RNA evidence was not identified.
BS4 No family data were identified showing lack of segregation with disease. Details ▾Hide ▴
Still missing
- Non-segregation evidence was not identified.
BP2 No phase data were identified showing this variant in trans with a pathogenic variant for a dominant disorder or in cis with a pathogenic variant. Details ▾Hide ▴
Still missing
- Phase information was not identified.
BP5 No independent alternate molecular explanation for a reported phenotype was identified. Details ▾Hide ▴
Still missing
- Case-level alternate-cause evidence was not identified.
BP6 Although ClinVar contains multiple benign submissions, BP6 was not separately applied because the benign classification itself is not treated here as independent criterion-level evidence beyond the underlying population and computational findings. Details ▾Hide ▴
Evidence considered
- ClinVar reports 14 clinical-laboratory benign submissions.
Sources
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis intronic c.1950+10C>T variant is outside the canonical +/-1,2 splice positions and does not fall into the generic null-variant categories used for default PVS1 application, so PVS1 is not applicable. Details ▾Hide ▴
Evidence considered
- Generic PVS1 fallback was considered because TERT loss of function is an established germline disease mechanism.
- The variant-specific PVS1 scaffold indicates c.1950+10C>T is not a canonical splice or other default null variant.
Sources
PS1 N/AThis is not a protein-coding substitution with an established amino acid change, so PS1 is not applicable. Details ▾Hide ▴
No further detail was recorded.
PM1 N/AThis intronic +10 variant is not located in a defined mutational hotspot or critical functional domain established for PM1 use. Details ▾Hide ▴
No further detail was recorded.
PM4 N/AThis intronic substitution does not produce a protein length change, so PM4 is not applicable. Details ▾Hide ▴
No further detail was recorded.
PM5 N/AThis variant does not have a defined missense residue context, and the PM5 review artifact did not support classic same-residue PM5 use, so PM5 is not applicable. Details ▾Hide ▴
Evidence considered
- PM5 candidate review found no safe classic same-residue comparator context for this intronic variant.
Sources
pm5_candidates
PP2 N/AThis is not a missense variant, so PP2 is not applicable. Details ▾Hide ▴
No further detail was recorded.
BS1 N/AAlthough the observed population frequency is also above the generic BS1 threshold of 0.3%, BA1 is already met at a stronger benign level, so BS1 is not separately applied to avoid double counting the same frequency evidence. Details ▾Hide ▴
Evidence considered
- Observed population frequency exceeds both BS1 and BA1 thresholds.
Sources
BP1 N/AThis is not a missense variant, so BP1 is not applicable. Details ▾Hide ▴
No further detail was recorded.
BP3 N/AThis intronic variant is not located in a repetitive region or described low-complexity region used for BP3 assessment. Details ▾Hide ▴
No further detail was recorded.
BP7 N/AThis is not a synonymous or deep intronic silent variant assessed under BP7 wording; instead, the relevant noncoding computational evidence was considered under BP4. Details ▾Hide ▴
Identifiers
- Gene
- TERT
- Transcript
- NM_198253.2
- Coding (HGVS c.)
- NM_198253.2:c.1950+10C>T
- Protein (HGVS p.)
- NP_937983.2:p.?
- GRCh38
- chr5:1280148 G>A
- GRCh37
- chr5:1280263 G>A
- ClinVar
- 227097, 4182821
- COSMIC
- COSV57245267
Gene diagram
Every interpreted variant in TERT, mapped onto the exon structure of NM_198253.2. Select a row to find it on the plot.
TERTNM_198253.2
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in TERT
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
19,637 / 1,614,020 alleles
AF 0.0122 · 187 homozygotes · FAF 0.024
gnomAD v2.1
3,864 / 282,560 alleles
AF 0.0137 · 49 homozygotes · FAF 0.024
gnomAD-Canada v1.0
201 / 18,412 alleles
AF 0.0109 · 1 homozygotes · FAF 0.0138
By genetic ancestry
gnomAD v4.1
AF 0.012 · 19637 / 1,614,020 alleles · 187 hom · FAF 0.024
| European (Finnish)2603 / 63,878 | 0.04165 hom |
| African/African American1870 / 75,060 | 0.02525 hom |
| Ashkenazi Jewish707 / 29,606 | 0.0249 hom |
| Remaining individuals754 / 62,508 | 0.0124 hom |
| European (non-Finnish)12934 / 1,179,994 | 0.01173 hom |
| Middle Eastern66 / 6,060 | 0.011 |
| Admixed American466 / 60,028 | 0.00783 hom |
| South Asian237 / 91,086 | 0.00268 hom |
0 alternate alleles recorded in 2 other groups: Amish, East Asian.
gnomAD v2.1
AF 0.014 · 3864 / 282,560 alleles · 49 hom · FAF 0.024
| European (Finnish)1040 / 25,120 | 0.04122 hom |
| African/African American618 / 24,952 | 0.0258 hom |
| Ashkenazi Jewish230 / 10,370 | 0.0222 hom |
| Remaining individuals105 / 7,226 | 0.015 |
| European (non-Finnish)1544 / 128,898 | 0.01210 hom |
| Admixed American251 / 35,426 | 0.00712 hom |
| South Asian76 / 30,616 | 0.00255 hom |
0 alternate alleles recorded in 1 other group: East Asian.
gnomAD-Canada
AF 0.011 · 201 / 18,412 alleles · 1 hom · FAF 0.014
| fin2 / 8 | 0.25 |
| asj19 / 832 | 0.0231 hom |
| mid3 / 144 | 0.021 |
| afr21 / 1,020 | 0.021 |
| oth15 / 1,138 | 0.013 |
| nfe129 / 11,732 | 0.011 |
| amr8 / 838 | 0.0095 |
| sas4 / 1,362 | 0.0029 |
0 alternate alleles recorded in 1 other group: eas.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.0121665; MAF= 1.21665%, 19637/1614020 alleles, homozygotes = 187) and has highest observed frequency in the European (Finnish) population (AF= 0.0407496; MAF= 4.07496%, 2603/63878 alleles, homozygotes = 65); grpmax FAF= 0.023973.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.013675; MAF= 1.36750%, 3864/282560 alleles, homozygotes = 49) and has highest observed frequency in the European (Finnish) population (AF= 0.0414013; MAF= 4.14013%, 1040/25120 alleles, homozygotes = 22); grpmax FAF= 0.0239814.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0109168; MAF= 1.09168%, 201/18412 alleles, homozygotes = 1) and has highest observed frequency in the afr population (AF= 0.0205882; grpmax FAF95= 0.013796).
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingAvailable computational evidence supports no meaningful impact on splicing. SpliceAI predicts no significant splice effect, with a maximum delta score of 0.07, which is below commonly used thresholds for splice disruption. Details ▾Hide ▴
PP3 Available computational evidence does not support a damaging effect on splicing. SpliceAI predicts no significant splice impact, with a maximum delta score of 0.07, which is below commonly used concern thresholds. Details ▾Hide ▴
Evidence considered
- SpliceAI DS_AG 0.00
- DS_AL 0.00
- DS_DG 0.05
- DS_DL 0.07
- max delta score 0.07.
Sources
BP7 N/AThis is not a synonymous or deep intronic silent variant assessed under BP7 wording; instead, the relevant noncoding computational evidence was considered under BP4. Details ▾Hide ▴
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07).
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
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PMID 22138009 ↗NCCN Task Force report: Evaluating the clinical utility of tumor markers in oncology.Febbo PG et al. · 2011No paper-specific finding is recorded.
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PMID 24033266 ↗A systematic approach to assessing the clinical significance of genetic variants.Duzkale H et al. · 2013No paper-specific finding is recorded.
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.No paper-specific finding is recorded.
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PMID 20301408 ↗Pulmonary Fibrosis Predisposition Overview.Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 20301779 ↗Dyskeratosis Congenita and Related Telomere Biology Disorders.Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 20963938 ↗CEBPA-Associated Familial Acute Myeloid Leukemia (AML).Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 23970018 ↗Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Fey MF et al. · 2013No paper-specific finding is recorded.
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PMID 32171751 ↗Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Heuser M et al. · 2020No paper-specific finding is recorded.
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
19,637 / 1,614,020 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.070
Open source ↗
ClinVar
14 Benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/227097/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/5-1280263-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr5-1280148-G-A?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/5-1280148-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_198253.2%3Ac.1950…
- OncoKB ↗www.oncokb.org/gene/TERT/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=127097585
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.0121665; MAF= 1.21665%, 19637/1614020 alleles, homozygotes = 187) and has highest observed frequency in the European (Finnish) population (AF= 0.0407496; MAF= 4.07496%, 2603/63878 alleles, homozygotes = 65); grpmax FAF= 0.023973.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.013675; MAF= 1.36750%, 3864/282560 alleles, homozygotes = 49) and has highest observed frequency in the European (Finnish) population (AF= 0.0414013; MAF= 4.14013%, 1040/25120 alleles, homozygotes = 22); grpmax FAF= 0.0239814.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0109168; MAF= 1.09168%, 201/18412 alleles, homozygotes = 1) and has highest observed frequency in the afr population (AF= 0.0205882; grpmax FAF95= 0.013796).
ClinVar
This variant has been reported in ClinVar as Benign (14 clinical laboratories). (ClinVarID = 227097)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07).
Somatic
This variant has previously been reported in somatic cancers (COSMIC; COSV57245267, n = 8 times).