rs34829399

Positions:

• chr5-1286887-G-A

Variant summary

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

The ENST00000310581.10(TERT):​c.1574-4263C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 152,042 control chromosomes in the GnomAD database, including 9 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 0.0025 (9 hom., cov: 32)
• Consequence: TERT ENST00000310581.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERT	NM_198253.3	c.1574-4263C>T		intron_variant		ENST00000310581.10	NP_937983.2
TERT	NM_001193376.3	c.1574-4263C>T		intron_variant			NP_001180305.1
TERT	NR_149162.3	n.1653-4263C>T		intron_variant, non_coding_transcript_variant
TERT	NR_149163.3	n.1653-4263C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TERT	ENST00000310581.10	c.1574-4263C>T		intron_variant		1	NM_198253.3	ENSP00000309572	P2
TERT	ENST00000334602.10	c.1574-4263C>T		intron_variant		1		ENSP00000334346	A2
TERT	ENST00000460137.6	c.1574-4263C>T		intron_variant, NMD_transcript_variant		1		ENSP00000425003
TERT	ENST00000656021.1	c.*397C>T		3_prime_UTR_variant, NMD_transcript_variant	3/17			ENSP00000499759

Frequencies

GnomAD3 genomes AF: 0.00249 AC: 378 AN: 151924 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000591

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0655

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00239

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

GnomAD4 genome AF: 0.00247 AC: 376 AN: 152042 Hom.: 9 Cov.: 32 AF XY: 0.00277 AC XY: 206 AN XY: 74316

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.000590

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0655

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00107 Hom.: 0

Bravo AF: 0.00283

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.67

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: rs34829399; hg19: chr5-1287002;