chr5-1255729-C-T

Position:

• chr5-1255729-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_198253.3(TERT):​c.3033-318G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00884 in 152,296 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0088 (7 hom., cov: 32)
• Consequence: TERT NM_198253.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.21

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 5-1255729-C-T is Benign according to our data. Variant chr5-1255729-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1218807.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00884 (1346/152296) while in subpopulation NFE AF= 0.0136 (922/67998). AF 95% confidence interval is 0.0128. There are 7 homozygotes in gnomad4. There are 678 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERT	NM_198253.3	c.3033-318G>A		intron_variant		ENST00000310581.10	NP_937983.2
TERT	NM_001193376.3	c.2844-318G>A		intron_variant			NP_001180305.1
TERT	NR_149162.3	n.2741-318G>A		intron_variant, non_coding_transcript_variant
TERT	NR_149163.3	n.2705-318G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TERT	ENST00000310581.10	c.3033-318G>A		intron_variant		1	NM_198253.3	ENSP00000309572	P2
	ENST00000666708.1	n.772C>T		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.00885 AC: 1347 AN: 152178 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00244

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0205

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.00908

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

GnomAD4 genome AF: 0.00884 AC: 1346 AN: 152296 Hom.: 7 Cov.: 32 AF XY: 0.00910 AC XY: 678 AN XY: 74468

Gnomad4 AFR AF: 0.00243

Gnomad4 AMR AF: 0.00516

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0205

Gnomad4 NFE AF: 0.0136

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.0102 Hom.: 0

Bravo AF: 0.00747

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
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: rs35387865; hg19: chr5-1255844;