4-109746231-G-T
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_000204.5(CFI):c.1420C>A(p.Arg474Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,568 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
CFI
NM_000204.5 synonymous
NM_000204.5 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.42
Genes affected
CFI (HGNC:5394): (complement factor I) This gene encodes a serine proteinase that is essential for regulating the complement cascade. The encoded preproprotein is cleaved to produce both heavy and light chains, which are linked by disulfide bonds to form a heterodimeric glycoprotein. This heterodimer can cleave and inactivate the complement components C4b and C3b, and it prevents the assembly of the C3 and C5 convertase enzymes. Defects in this gene cause complement factor I deficiency, an autosomal recessive disease associated with a susceptibility to pyogenic infections. Mutations in this gene have been associated with a predisposition to atypical hemolytic uremic syndrome, a disease characterized by acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. Primary glomerulonephritis with immune deposits and age-related macular degeneration are other conditions associated with mutations of this gene. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP7
Synonymous conserved (PhyloP=2.41 with no splicing effect.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CFI | ENST00000394634.7 | c.1420C>A | p.Arg474Arg | synonymous_variant | Exon 11 of 13 | 1 | NM_000204.5 | ENSP00000378130.2 | ||
| ENSG00000285330 | ENST00000645635.1 | c.1420C>A | p.Arg474Arg | synonymous_variant | Exon 11 of 15 | ENSP00000493607.1 |
Frequencies
GnomAD3 genomes 0.00000659 AC: 1AN: 151778Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461790Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727198
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GnomAD4 genome 0.00000659 AC: 1AN: 151778Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74074
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ClinVar
Not reported inComputational scores
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Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at