rs7725218

Positions:

• chr5-1282299-G-A
• chr5-1282299-G-T

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.1769+130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 955,560 control chromosomes in the GnomAD database, including 60,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (10717 hom., cov: 33)
  • Exomes 𝑓: 0.35 (50075 hom.)
• Consequence: TERT NM_198253.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.977

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=-0.89).
• BP6: Variant 5-1282299-G-A is Benign according to our data. Variant chr5-1282299-G-A is described in ClinVar as [Benign]. Clinvar id is 1280138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERT	NM_198253.3	c.1769+130C>T		intron_variant		ENST00000310581.10
TERT	NM_001193376.3	c.1769+130C>T		intron_variant
TERT	NR_149162.3	n.1848+130C>T		intron_variant, non_coding_transcript_variant
TERT	NR_149163.3	n.1848+130C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERT	ENST00000310581.10	c.1769+130C>T		intron_variant		1	NM_198253.3	P2

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57018 AN: 151948 Hom.: 10704 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.410

GnomAD4 exome AF: 0.349 AC: 280301 AN: 803494 Hom.: 50075 AF XY: 0.352 AC XY: 148187 AN XY: 420532

Gnomad4 AFR exome AF: 0.427

Gnomad4 AMR exome AF: 0.292

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.364

Gnomad4 SAS exome AF: 0.412

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.336

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.375 AC: 57063 AN: 152066 Hom.: 10717 Cov.: 33 AF XY: 0.373 AC XY: 27714 AN XY: 74346

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.418

Alfa AF: 0.361 Hom.: 2956

Bravo AF: 0.375

Asia WGS AF: 0.449 AC: 1564 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	-0.89
CADD	Benign	0.44
DANN	Benign	0.51

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: rs7725218; hg19: chr5-1282414; COSMIC: COSV57204890;