rs79588315
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_018062.4(FANCL):c.217-11T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0837 in 1,605,374 control chromosomes in the GnomAD database, including 6,241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.065 ( 408 hom., cov: 32)
Exomes 𝑓: 0.086 ( 5833 hom. )
Consequence
FANCL
NM_018062.4 splice_polypyrimidine_tract, intron
NM_018062.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.7185
2
Clinical Significance
Conservation
PhyloP100: 1.73
Genes affected
FANCL (HGNC:20748): (FA complementation group L) This gene encodes a ubiquitin ligase that is a member of the Fanconi anemia complementation group (FANC). Members of this group are related by their assembly into a common nuclear protein complex rather than by sequence similarity. This gene encodes the protein for complementation group L that mediates monoubiquitination of FANCD2 as well as FANCI. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2018]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
Variant 2-58226795-A-G is Benign according to our data. Variant chr2-58226795-A-G is described in ClinVar as [Benign]. Clinvar id is 257493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCL | NM_018062.4 | c.217-11T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000233741.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCL | ENST00000233741.9 | c.217-11T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_018062.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0646 AC: 9826AN: 152106Hom.: 408 Cov.: 32
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GnomAD3 exomes AF: 0.0678 AC: 16983AN: 250540Hom.: 711 AF XY: 0.0691 AC XY: 9354AN XY: 135388
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GnomAD4 exome AF: 0.0857 AC: 124516AN: 1453148Hom.: 5833 Cov.: 30 AF XY: 0.0847 AC XY: 61245AN XY: 723394
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GnomAD4 genome ? AF: 0.0645 AC: 9824AN: 152226Hom.: 408 Cov.: 32 AF XY: 0.0628 AC XY: 4672AN XY: 74434
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fanconi anemia complementation group L Benign:2
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 10, 2019 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 48
DS_AL_spliceai
Position offset: -11
Find out detailed SpliceAI scores and Pangolin per-transcript scores at