5-1286362-G-T

Position:

• chr5-1286362-G-T

Variant summary

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

The ENST00000310581.10(TERT):​c.1574-3738C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 152,256 control chromosomes in the GnomAD database, including 10 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 0.010 (10 hom., cov: 31)
• Consequence: TERT ENST00000310581.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

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=-0.93).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0105 (1593/152256) while in subpopulation NFE AF= 0.0159 (1084/68032). AF 95% confidence interval is 0.0151. There are 10 homozygotes in gnomad4. There are 740 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERT	NM_198253.3	c.1574-3738C>A		intron_variant		ENST00000310581.10	NP_937983.2
TERT	NM_001193376.3	c.1574-3738C>A		intron_variant			NP_001180305.1
TERT	NR_149162.3	n.1653-3738C>A		intron_variant, non_coding_transcript_variant
TERT	NR_149163.3	n.1653-3738C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TERT	ENST00000310581.10	c.1574-3738C>A		intron_variant		1	NM_198253.3	ENSP00000309572	P2
TERT	ENST00000334602.10	c.1574-3738C>A		intron_variant		1		ENSP00000334346	A2
TERT	ENST00000460137.6	c.1574-3738C>A		intron_variant, NMD_transcript_variant		1		ENSP00000425003
TERT	ENST00000656021.1	c.*922C>A		3_prime_UTR_variant, NMD_transcript_variant	3/17			ENSP00000499759

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1594 AN: 152138 Hom.: 10 Cov.: 31

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.00382

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

GnomAD4 genome AF: 0.0105 AC: 1593 AN: 152256 Hom.: 10 Cov.: 31 AF XY: 0.00994 AC XY: 740 AN XY: 74442

Gnomad4 AFR AF: 0.00298

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.0105 Hom.: 1

Bravo AF: 0.00875

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.31
DANN	Benign	0.52

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: rs34363858; hg19: chr5-1286477;