rs2853672

Positions:

• chr5-1292868-C-A
• chr5-1292868-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198253.3(TERT):​c.1573+445G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,032 control chromosomes in the GnomAD database, including 18,486 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18486 hom., cov: 33)
• Consequence: TERT NM_198253.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERT	NM_198253.3	c.1573+445G>T		intron_variant		ENST00000310581.10
TERT	NM_001193376.3	c.1573+445G>T		intron_variant
TERT	NR_149162.3	n.1652+445G>T		intron_variant, non_coding_transcript_variant
TERT	NR_149163.3	n.1652+445G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERT	ENST00000310581.10	c.1573+445G>T		intron_variant		1	NM_198253.3	P2
TERT	ENST00000334602.10	c.1573+445G>T		intron_variant		1		A2
TERT	ENST00000460137.6	c.1573+445G>T		intron_variant, NMD_transcript_variant		1
TERT	ENST00000656021.1	c.*197+96G>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74571 AN: 151914 Hom.: 18470 Cov.: 33

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.491 AC: 74628 AN: 152032 Hom.: 18486 Cov.: 33 AF XY: 0.493 AC XY: 36619 AN XY: 74308

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.455

Alfa AF: 0.471 Hom.: 20142

Bravo AF: 0.498

Asia WGS AF: 0.434 AC: 1509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2853672; hg19: chr5-1292983;