rs45556032
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_022725.4(FANCF):c.387C>T(p.Leu129=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00927 in 1,614,150 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0073 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0095 ( 83 hom. )
Consequence
FANCF
NM_022725.4 synonymous
NM_022725.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.60
Genes affected
FANCF (HGNC:3587): (FA complementation group F) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group F. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 11-22625424-G-A is Benign according to our data. Variant chr11-22625424-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22625424-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.6 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00728 (1110/152370) while in subpopulation NFE AF= 0.0112 (762/68030). AF 95% confidence interval is 0.0105. There are 5 homozygotes in gnomad4. There are 550 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCF | NM_022725.4 | c.387C>T | p.Leu129= | synonymous_variant | 1/1 | ENST00000327470.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCF | ENST00000327470.6 | c.387C>T | p.Leu129= | synonymous_variant | 1/1 | NM_022725.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00729 AC: 1110AN: 152252Hom.: 5 Cov.: 33
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GnomAD3 exomes AF: 0.00706 AC: 1764AN: 249956Hom.: 9 AF XY: 0.00708 AC XY: 961AN XY: 135706
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GnomAD4 exome AF: 0.00947 AC: 13848AN: 1461780Hom.: 83 Cov.: 32 AF XY: 0.00926 AC XY: 6731AN XY: 727192
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GnomAD4 genome ? AF: 0.00728 AC: 1110AN: 152370Hom.: 5 Cov.: 33 AF XY: 0.00738 AC XY: 550AN XY: 74506
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 27, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 03, 2022 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | FANCF: BP4, BP7, BS1, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 02, 2021 | - - |
Fanconi anemia complementation group F Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Fanconi anemia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at