rs373879259
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_198253.3(TERT):c.2130+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,567,898 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_198253.3 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.2130+10G>A | intron_variant | Intron 5 of 15 | ENST00000310581.10 | NP_937983.2 | ||
TERT | NM_001193376.3 | c.2130+10G>A | intron_variant | Intron 5 of 14 | NP_001180305.1 | |||
TERT | NR_149162.3 | n.2209+10G>A | intron_variant | Intron 5 of 12 | ||||
TERT | NR_149163.3 | n.2209+10G>A | intron_variant | Intron 5 of 12 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000460 AC: 70AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000124 AC: 22AN: 177130Hom.: 0 AF XY: 0.000114 AC XY: 11AN XY: 96290
GnomAD4 exome AF: 0.0000721 AC: 102AN: 1415570Hom.: 1 Cov.: 33 AF XY: 0.0000700 AC XY: 49AN XY: 700038
GnomAD4 genome AF: 0.000453 AC: 69AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.000349 AC XY: 26AN XY: 74478
ClinVar
Submissions by phenotype
not specified Uncertain:1
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Aplastic anemia Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Dyskeratosis congenita, autosomal dominant 2 Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Dyskeratosis congenita Uncertain:1
The c.2130+10G>A intronic variant results from a G to A substitution 10 nucleotides after coding exon 5 in the TERT gene. This variant was previously reported in the SNPDatabase as rs373879259. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.03% (4/12840) total alleles studied, having been observed in 0.07% (3/4328) African American alleles and 0.01% (1/8512) European American alleles. This nucleotide position is well conserved on limited sequence alignment. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of c.2130+10G>A remains unclear. -
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
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Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
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TERT-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at