Variant 5-1280362-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198253.3(TERT):c.1770-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,609,006 control chromosomes in the GnomAD database, including 13,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1122 hom., cov: 33)

Exomes 𝑓: 0.13 ( 12137 hom. )

Consequence

TERT
NM_198253.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0530

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]

TERT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 5-1280362-G-A is Benign according to our data. Variant chr5-1280362-G-A is described in ClinVar as [Benign]. Clinvar id is 1274097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
TERT	NM_198253.3 linkuse as main transcript	c.1770-24C>T	intron_variant	ENST00000310581.10	NP_937983.2
TERT	NM_001193376.3 linkuse as main transcript	c.1770-24C>T	intron_variant		NP_001180305.1
TERT	NR_149162.3 linkuse as main transcript	n.1849-24C>T	intron_variant, non_coding_transcript_variant
TERT	NR_149163.3 linkuse as main transcript	n.1849-24C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TERT	ENST00000310581.10 linkuse as main transcript	c.1770-24C>T		intron_variant		1	NM_198253.3	ENSP00000309572	P2	O14746-1

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16304

AN:

152132

Hom.:

1106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0357

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.0956

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.127

AC:

31040

AN:

243860

Hom.:

2160

AF XY:

0.126

AC XY:

16801

AN XY:

132880

show subpopulations

Gnomad AFR exome

AF:

0.0324

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.209

Gnomad SAS exome

AF:

0.0993

Gnomad FIN exome

AF:

0.158

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.126

AC:

183570

AN:

1456754

Hom.:

12137

Cov.:

AF XY:

0.126

AC XY:

91120

AN XY:

724744

show subpopulations

Gnomad4 AFR exome

AF:

0.0328

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.160

Gnomad4 SAS exome

AF:

0.100

Gnomad4 FIN exome

AF:

0.156

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.107

AC:

16342

AN:

152252

Hom.:

1122

Cov.:

AF XY:

0.107

AC XY:

7943

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0360

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.129

Gnomad4 EAS

AF:

0.208

Gnomad4 SAS

AF:

0.0963

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.129

Hom.:

488

Bravo

AF:

0.103

Asia WGS

AF:

0.179

AC:

621

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.4

DANN

Benign

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over