rs3823434
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_021922.3(FANCE):c.1071C>T(p.Leu357=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 1,614,144 control chromosomes in the GnomAD database, including 1,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.027 ( 102 hom., cov: 32)
Exomes 𝑓: 0.030 ( 1245 hom. )
Consequence
FANCE
NM_021922.3 synonymous
NM_021922.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.281
Genes affected
FANCE (HGNC:3586): (FA complementation group E) 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 E. [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=-0.6).
BP6
?
Variant 6-35458398-C-T is Benign according to our data. Variant chr6-35458398-C-T is described in ClinVar as [Benign]. Clinvar id is 261432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-35458398-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.281 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCE | NM_021922.3 | c.1071C>T | p.Leu357= | synonymous_variant | 5/10 | ENST00000229769.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCE | ENST00000229769.3 | c.1071C>T | p.Leu357= | synonymous_variant | 5/10 | 1 | NM_021922.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0274 AC: 4173AN: 152166Hom.: 102 Cov.: 32
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GnomAD3 exomes AF: 0.0402 AC: 10114AN: 251482Hom.: 368 AF XY: 0.0407 AC XY: 5526AN XY: 135916
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GnomAD4 exome AF: 0.0303 AC: 44305AN: 1461860Hom.: 1245 Cov.: 32 AF XY: 0.0315 AC XY: 22889AN XY: 727236
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GnomAD4 genome ? AF: 0.0274 AC: 4169AN: 152284Hom.: 102 Cov.: 32 AF XY: 0.0301 AC XY: 2241AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fanconi anemia complementation group E Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
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. - |
not provided Uncertain:1Benign:1
Uncertain significance, no assertion criteria provided | curation | Leiden Open Variation Database | Feb 07, 2011 | Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 14, 2019 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
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