rs7705526

chr5-1285859-C-Achr5-1285859-C-Gchr5-1285859-C-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.1574-3235G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,526 control chromosomes in the GnomAD database, including 6,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (6736 hom., cov: 29)
• Consequence: TERT NM_198253.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.498

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=-0.96).
• BP6: Variant 5-1285859-C-A is Benign according to our data. Variant chr5-1285859-C-A is described in ClinVar as [Benign]. Clinvar id is 539227.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERT	NM_198253.3	c.1574-3235G>T		intron_variant		ENST00000310581.10
TERT	NM_001193376.3	c.1574-3235G>T		intron_variant
TERT	NR_149162.3	n.1653-3235G>T		intron_variant, non_coding_transcript_variant
TERT	NR_149163.3	n.1653-3235G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERT	ENST00000310581.10	c.1574-3235G>T		intron_variant		1	NM_198253.3	P2
TERT	ENST00000334602.10	c.1574-3235G>T		intron_variant		1		A2
TERT	ENST00000460137.6	c.1574-3235G>T		intron_variant, NMD_transcript_variant		1
TERT	ENST00000656021.1	c.*1119+306G>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44209 AN: 151408 Hom.: 6729 Cov.: 29

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.292 AC: 44226 AN: 151526 Hom.: 6736 Cov.: 29 AF XY: 0.291 AC XY: 21553 AN XY: 74004

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.356

Alfa AF: 0.279 Hom.: 1605

Bravo AF: 0.284

Asia WGS AF: 0.435 AC: 1512 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dyskeratosis congenita, autosomal dominant 2;C5561926:Interstitial lung disease 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 04, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.27
Dann	Benign	0.57

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: rs7705526; hg19: chr5-1285974;