rs775216604
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001018113.3(FANCB):āc.510T>Gā(p.Ile170Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,209,182 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict 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. I170V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001018113.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCB | NM_001018113.3 | c.510T>G | p.Ile170Met | missense_variant | 3/10 | ENST00000650831.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCB | ENST00000650831.1 | c.510T>G | p.Ile170Met | missense_variant | 3/10 | NM_001018113.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000269 AC: 3AN: 111442Hom.: 0 Cov.: 24 AF XY: 0.0000297 AC XY: 1AN XY: 33628
GnomAD3 exomes AF: 0.0000437 AC: 8AN: 183104Hom.: 0 AF XY: 0.0000295 AC XY: 2AN XY: 67722
GnomAD4 exome AF: 0.0000465 AC: 51AN: 1097740Hom.: 0 Cov.: 31 AF XY: 0.0000468 AC XY: 17AN XY: 363142
GnomAD4 genome ? AF: 0.0000269 AC: 3AN: 111442Hom.: 0 Cov.: 24 AF XY: 0.0000297 AC XY: 1AN XY: 33628
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 30, 2021 | This sequence change does not appear to have been previously described in patients with FANCB-related disorders and has been described in the gnomAD database with a low population frequency of 0.0097% in the non-Finnish European subpopulation (dbSNP rs775216604). The p.Ile170Met change affects a moderately conserved amino acid residue located in a domain of the FANCB protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Ile170Met substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Ile170Met change remains unknown at this time. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 05, 2023 | 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. - |
Fanconi anemia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at