rs10069690

Positions:

• chr5-1279675-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_198253.3(TERT):​c.1951-205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,058 control chromosomes in the GnomAD database, including 10,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.35 (10955 hom., cov: 33)
• Consequence: TERT NM_198253.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -1.93

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 -16 ACMG points.

• BP6: Variant 5-1279675-C-T is Benign according to our data. Variant chr5-1279675-C-T is described in ClinVar as [Benign]. Clinvar id is 225783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERT	NM_198253.3	c.1951-205G>A		intron_variant		ENST00000310581.10	NP_937983.2
TERT	NM_001193376.3	c.1951-205G>A		intron_variant			NP_001180305.1
TERT	NR_149162.3	n.2030-205G>A		intron_variant, non_coding_transcript_variant
TERT	NR_149163.3	n.2030-205G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TERT	ENST00000310581.10	c.1951-205G>A		intron_variant		1	NM_198253.3	ENSP00000309572	P2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53038 AN: 151940 Hom.: 10937 Cov.: 33

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.337

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.349 AC: 53094 AN: 152058 Hom.: 10955 Cov.: 33 AF XY: 0.346 AC XY: 25703 AN XY: 74334

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.335

Alfa AF: 0.275 Hom.: 8912

Bravo AF: 0.353

Asia WGS AF: 0.257 AC: 899 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 24, 2018	This variant is associated with the following publications: (PMID: 26143636, 25919761, 26053551, 23535731, 22037553, 23066086) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Chronic osteomyelitis Other:1

association, no assertion criteria provided

case-control

Department of Orthopeadics and Traumatology, Nanfang Hospital

Sep 01, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.8
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: 3

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

Publications

LitVar

Other links and lift over

dbSNP: rs10069690; hg19: chr5-1279790;