chr6-109691462-C-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_014845.6(FIG4):c.27C>T(p.Ile9Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00505 in 1,586,892 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_014845.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00390 AC: 593AN: 152210Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00477 AC: 968AN: 202902Hom.: 6 AF XY: 0.00492 AC XY: 539AN XY: 109518
GnomAD4 exome AF: 0.00518 AC: 7425AN: 1434564Hom.: 40 Cov.: 31 AF XY: 0.00526 AC XY: 3742AN XY: 710944
GnomAD4 genome AF: 0.00389 AC: 592AN: 152328Hom.: 1 Cov.: 32 AF XY: 0.00372 AC XY: 277AN XY: 74486
ClinVar
Submissions by phenotype
not specified Benign:6
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. -
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not provided Benign:4
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FIG4: BP4, BS2 -
Charcot-Marie-Tooth disease Benign:1
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Amyotrophic lateral sclerosis type 11 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. -
Charcot-Marie-Tooth disease type 4J 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. -
FIG4-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Yunis-Varon syndrome;C1970011:Charcot-Marie-Tooth disease type 4J;C2675491:Amyotrophic lateral sclerosis type 11;C4013648:Bilateral parasagittal parieto-occipital polymicrogyria Benign:1
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Charcot-Marie-Tooth disease type 4 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at