5-1260080-T-C

Position:

• chr5-1260080-T-C

Variant summary

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

The NM_198253.3(TERT):​c.2970+394A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,144 control chromosomes in the GnomAD database, including 9,889 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 0.33 (9889 hom., cov: 34)
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERT	NM_198253.3	c.2970+394A>G		intron_variant		ENST00000310581.10
TERT	NM_001193376.3	c.2781+394A>G		intron_variant
TERT	NR_149162.3	n.2678+394A>G		intron_variant, non_coding_transcript_variant
TERT	NR_149163.3	n.2642+394A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERT	ENST00000310581.10	c.2970+394A>G		intron_variant		1	NM_198253.3	P2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49550 AN: 152026 Hom.: 9866 Cov.: 34

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.326 AC: 49617 AN: 152144 Hom.: 9889 Cov.: 34 AF XY: 0.317 AC XY: 23605 AN XY: 74394

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0795

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.268

Alfa AF: 0.313 Hom.: 1438

Bravo AF: 0.337

Asia WGS AF: 0.179 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2736118; hg19: chr5-1260195;