5-1280013-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_198253.3(TERT):c.1950+145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,079,128 control chromosomes in the GnomAD database, including 102,532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (18906 hom., cov: 34)
  • Exomes 𝑓: 0.42 (83626 hom.)
• Consequence: TERT NM_198253.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.819

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 -10 ACMG points.

• BP6: Variant 5-1280013-T-C is Benign according to our data. Variant chr5-1280013-T-C is described in ClinVar as [Benign]. Clinvar id is 1267625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERT	NM_198253.3	c.1950+145A>G		intron_variant		ENST00000310581.10
TERT	NM_001193376.3	c.1950+145A>G		intron_variant
TERT	NR_149162.3	n.2029+145A>G		intron_variant, non_coding_transcript_variant
TERT	NR_149163.3	n.2029+145A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERT	ENST00000310581.10	c.1950+145A>G		intron_variant		1	NM_198253.3	P2

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74016 AN: 152026 Hom.: 18867 Cov.: 34

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.489

GnomAD4 exome AF: 0.419 AC: 388845 AN: 926984 Hom.: 83626 AF XY: 0.418 AC XY: 199137 AN XY: 476470

Gnomad4 AFR exome AF: 0.668

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.456

Gnomad4 EAS exome AF: 0.374

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.458

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.435

GnomAD4 genome AF: 0.487 AC: 74109 AN: 152144 Hom.: 18906 Cov.: 34 AF XY: 0.482 AC XY: 35877 AN XY: 74382

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.496

Alfa AF: 0.448 Hom.: 3565

Bravo AF: 0.488

Asia WGS AF: 0.455 AC: 1585 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	7.7
Dann	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.26		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7734992; hg19: chr5-1280128; COSMIC: COSV57212982;