5-1292003-G-A

Position:

• chr5-1292003-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_198253.3(TERT):​c.1573+1310C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 152,308 control chromosomes in the GnomAD database, including 51 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 0.020 (51 hom., cov: 32)
• Consequence: TERT NM_198253.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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=-0.8).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0196 (2990/152308) while in subpopulation NFE AF= 0.029 (1970/68028). AF 95% confidence interval is 0.0279. There are 51 homozygotes in gnomad4. There are 1470 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 51 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERT	NM_198253.3	c.1573+1310C>T		intron_variant		ENST00000310581.10
TERT	NM_001193376.3	c.1573+1310C>T		intron_variant
TERT	NR_149162.3	n.1652+1310C>T		intron_variant, non_coding_transcript_variant
TERT	NR_149163.3	n.1652+1310C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERT	ENST00000310581.10	c.1573+1310C>T		intron_variant		1	NM_198253.3	P2
TERT	ENST00000334602.10	c.1573+1310C>T		intron_variant		1		A2
TERT	ENST00000460137.6	c.1573+1310C>T		intron_variant, NMD_transcript_variant		1
TERT	ENST00000656021.1	c.*197+961C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2989 AN: 152190 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.00410

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0606

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0289

Gnomad OTH AF: 0.0125

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

GnomAD4 genome AF: 0.0196 AC: 2990 AN: 152308 Hom.: 51 Cov.: 32 AF XY: 0.0197 AC XY: 1470 AN XY: 74472

Gnomad4 AFR AF: 0.00409

Gnomad4 AMR AF: 0.00706

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0606

Gnomad4 NFE AF: 0.0290

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0250 Hom.: 19

Bravo AF: 0.0146

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.81

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: rs71595003; hg19: chr5-1292118;