rs13167280

chr5-1280362-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0530

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERT	NM_198253.3	c.1770-24C>T		intron_variant		ENST00000310581.10
TERT	NM_001193376.3	c.1770-24C>T		intron_variant
TERT	NR_149162.3	n.1849-24C>T		intron_variant, non_coding_transcript_variant
TERT	NR_149163.3	n.1849-24C>T		intron_variant, non_coding_transcript_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16304 AN: 152132 Hom.: 1106 Cov.: 33

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

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.: 32 AF XY: 0.126 AC XY: 91120 AN XY: 724744

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.: 33 AF XY: 0.107 AC XY: 7943 AN XY: 74432

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs13167280; hg19: chr5-1280477; COSMIC: COSV57198812;