X-14850514-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001018113.3(FANCB):c.1487C>G(p.Ser496Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000276 in 1,087,126 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S496F) has been classified as Uncertain significance.
Frequency
Consequence
NM_001018113.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCB | NM_001018113.3 | c.1487C>G | p.Ser496Cys | missense_variant | 7/10 | ENST00000650831.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCB | ENST00000650831.1 | c.1487C>G | p.Ser496Cys | missense_variant | 7/10 | NM_001018113.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD4 exome AF: 0.00000276 AC: 3AN: 1087126Hom.: 0 Cov.: 28 AF XY: 0.00000283 AC XY: 1AN XY: 353580
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 02, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FANCB-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with cysteine at codon 496 of the FANCB protein (p.Ser496Cys). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and cysteine. - |
Fanconi anemia complementation group B;C2931228:VACTERL association, X-linked, with or without hydrocephalus Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 13, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at