Classification rationale

BA1BP4 Benign

TERT c.1950+10C>T

The TERT c.1950+10C>T (p.?) variant has been reported in ClinVar as Benign by 14 clinical laboratories.¹ 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.² In silico splice prediction does not support a clinically meaningful splicing effect, with SpliceAI showing a maximum delta score of 0.07.³

BA1 + BP4 → Benign

1 clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗

3 spliceai ↗

Gene diagram · NM_198253.2 · variants mapped to exon structure

TERT NM_198253.2

Fetching transcript structure from UCSC…

Applied criteria · 2 met · select any tile

Met

Not met

Not assessed

N/A

Strength very strong supporting

Pathogenic evidence

PVS

PS

PM

PP

Benign evidence

BA

BS

BP

—

Rationale

Select a criterion.

Sources

Evidence used

Gaps remaining

Rule

—

Research & evidence

Population frequency · supports benign

gnomAD v4.1

gnomAD v2.1

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.

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.

🇨🇦 CA

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).

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

1.2% · 19637 / 1,614,020
187 hom · FAF 2.4%

European (Finnish) 2603 / 63,878	4.1% 65 hom
African/African American 1870 / 75,060	2.5% 25 hom
Ashkenazi Jewish 707 / 29,606	2.4% 9 hom
Remaining individuals 754 / 62,508	1.2% 4 hom
European (non-Finnish) 12934 / 1,179,994	1.1% 73 hom
Middle Eastern 66 / 6,060	1.1%
Admixed American 466 / 60,028	0.78% 3 hom
South Asian 237 / 91,086	0.26% 8 hom

+ 2 not observed (Amish, East Asian)

gnomAD v2.1

1.4% · 3864 / 282,560
49 hom · FAF 2.4%

European (Finnish) 1040 / 25,120	4.1% 22 hom
African/African American 618 / 24,952	2.5% 8 hom
Ashkenazi Jewish 230 / 10,370	2.2% 2 hom
Remaining individuals 105 / 7,226	1.5%
European (non-Finnish) 1544 / 128,898	1.2% 10 hom
Admixed American 251 / 35,426	0.71% 2 hom
South Asian 76 / 30,616	0.25% 5 hom

+ 1 not observed (East Asian)

gnomAD Canada 🇨🇦

1.1% · 201 / 18,412
1 hom · FAF 1.4%

indel · split

European (Finnish) 2 / 8	25%
Ashkenazi Jewish 19 / 832	2.3% 1 hom
Middle Eastern 3 / 144	2.1%
African/African American 21 / 1,020	2.1%
Remaining individuals 15 / 1,138	1.3%
European (non-Finnish) 129 / 11,732	1.1%
Latino/Admixed American 8 / 838	0.95%
South Asian 4 / 1,362	0.29%

+ 1 not observed (East Asian)

gnomAD v4 ↗ gnomAD v2 ↗ gnomAD 🇨🇦 ↗

ClinVar

This variant has been reported in ClinVar as Benign (14 clinical laboratories). (ClinVarID = 227097)

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07).

SpliceAI ↗

Functional No data

No calibrated functional assay or RNA evidence was identified for this variant.

OncoKB ↗

COSMIC

Somatic evidence

COSMIC

This variant has previously been reported in somatic cancers (COSMIC; COSV57245267, n = 8 times).

Hotspots

This variant does not lie in a statistically significant cancer hotspot.

COSMIC ↗

Sources & reference links

7Sources

ClinVar

gnomAD v2.1

gnomAD v4.1

gnomAD-Canada

SpliceAI

OncoKB

COSMIC

Triaged references · 9 PMIDs not cited in assessment

22138009 ↗ NCCN Task Force report: Evaluating the clinical utility of tumor markers in oncology. CLINVAR

24033266 ↗ A systematic approach to assessing the clinical significance of genetic variants. CLINVAR

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. CLINVAR

20301408 ↗ Pulmonary Fibrosis Predisposition Overview. CLINVAR

20301779 ↗ Dyskeratosis Congenita and Related Telomere Biology Disorders. CLINVAR

20963938 ↗ CEBPA-Associated Familial Acute Myeloid Leukemia (AML). CLINVAR

23970018 ↗ Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. CLINVAR

32171751 ↗ Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. CLINVAR

28492532 ↗ Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. CLINVAR