4-109746417-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BP6
The NM_000204.5(CFI):c.1234G>A(p.Val412Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V412E) has been classified as Uncertain significance.
Frequency
Consequence
NM_000204.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CFI | ENST00000394634.7 | c.1234G>A | p.Val412Met | missense_variant | Exon 11 of 13 | 1 | NM_000204.5 | ENSP00000378130.2 | ||
ENSG00000285330 | ENST00000645635.1 | c.1234G>A | p.Val412Met | missense_variant | Exon 11 of 15 | ENSP00000493607.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152020Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251316Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135818
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461706Hom.: 0 Cov.: 32 AF XY: 0.0000344 AC XY: 25AN XY: 727176
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74392
ClinVar
Submissions by phenotype
Atypical hemolytic-uremic syndrome with I factor anomaly;C3463916:Factor I deficiency;C3809523:Age related macular degeneration 13 Uncertain: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. -
Age related macular degeneration 13 Benign:1
This variant (GRCh38; NM_000204.5:c.1234G>A:p.Val412Met) results in a missense mutation with the conversion of Valine (Nonpolar amino acid) to Methionine (Nonpolar amino acid) in the CFI protein. Not observed at significant frequency in large population cohorts (gnomAD). Multiple lines of computational evidence of this variant suggest no impact on gene or gene product. Reputable source recently reports variant as benign. This variant is associated with the following publications: PubMed: 25986072, 31635417 Based on conflicting evidence or insufficient data to determine whether the variant is benign or pathogenic, the clinical significance of this alteration remains unclear. In summary, this variant meets our criteria for classification as of Unknown Clinical Significance based on the evidence outlined. -
not provided Benign:1
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Macular degeneration, age-related, 13, susceptibility to Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at