rs45442896
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000548.5(TSC2):c.848+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000653 in 1,551,680 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000548.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00344 AC: 524AN: 152198Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000767 AC: 120AN: 156540Hom.: 1 AF XY: 0.000534 AC XY: 44AN XY: 82412
GnomAD4 exome AF: 0.000348 AC: 487AN: 1399364Hom.: 6 Cov.: 32 AF XY: 0.000325 AC XY: 224AN XY: 690204
GnomAD4 genome AF: 0.00345 AC: 526AN: 152316Hom.: 3 Cov.: 32 AF XY: 0.00308 AC XY: 229AN XY: 74470
ClinVar
Submissions by phenotype
not specified Benign:4
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Tuberous sclerosis 2 Benign:2
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not provided Benign:2
TSC2: BP4, BS1, BS2 -
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Tuberous sclerosis syndrome Benign:1Other:1
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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. -
Hereditary cancer-predisposing syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at