rs7713218

chr5-1283197-A-Cchr5-1283197-A-Gchr5-1283197-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198253.3(TERT):c.1574-573T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000773 in 116,504 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000077 (0 hom., cov: 18)
• Consequence: TERT NM_198253.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERT	NM_198253.3	c.1574-573T>G		intron_variant		ENST00000310581.10
TERT	NM_001193376.3	c.1574-573T>G		intron_variant
TERT	NR_149162.3	n.1653-573T>G		intron_variant, non_coding_transcript_variant
TERT	NR_149163.3	n.1653-573T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERT	ENST00000310581.10	c.1574-573T>G		intron_variant		1	NM_198253.3	P2
TERT	ENST00000334602.10	c.1574-573T>G		intron_variant		1		A2
TERT	ENST00000460137.6	c.1574-573T>G		intron_variant, NMD_transcript_variant		1
TERT	ENST00000656021.1	c.*1120-573T>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0000773 AC: 9 AN: 116432 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.0000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000819

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000285

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000897

Gnomad OTH AF: 0.000613

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

GnomAD4 genome AF: 0.0000773 AC: 9 AN: 116504 Hom.: 0 Cov.: 18 AF XY: 0.0000710 AC XY: 4 AN XY: 56376

Gnomad4 AFR AF: 0.0000337

Gnomad4 AMR AF: 0.0000819

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000286

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000897

Gnomad4 OTH AF: 0.000608

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	2.3
Dann	Benign	0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7713218; hg19: chr5-1283312;