15-89260812-C-T
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_001113378.2(FANCI):c.257C>T(p.Ala86Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 1,612,532 control chromosomes in the GnomAD database, including 112,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.30 ( 8212 hom., cov: 32)
Exomes 𝑓: 0.37 ( 103813 hom. )
Consequence
FANCI
NM_001113378.2 missense
NM_001113378.2 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 2.06
Genes affected
FANCI (HGNC:25568): (FA complementation group I) 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 I. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 15-89260812-C-T is Benign according to our data. Variant chr15-89260812-C-T is described in ClinVar as [Benign]. Clinvar id is 257484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FANCI | NM_001113378.2 | c.257C>T | p.Ala86Val | missense_variant | 4/38 | ENST00000310775.12 | NP_001106849.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FANCI | ENST00000310775.12 | c.257C>T | p.Ala86Val | missense_variant | 4/38 | 1 | NM_001113378.2 | ENSP00000310842 | P1 |
Frequencies
GnomAD3 genomes AF: 0.299 AC: 45344AN: 151798Hom.: 8212 Cov.: 32
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GnomAD3 exomes AF: 0.360 AC: 90634AN: 251442Hom.: 17425 AF XY: 0.369 AC XY: 50097AN XY: 135900
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GnomAD4 exome AF: 0.372 AC: 543699AN: 1460616Hom.: 103813 Cov.: 39 AF XY: 0.374 AC XY: 271711AN XY: 726696
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GnomAD4 genome AF: 0.298 AC: 45337AN: 151916Hom.: 8212 Cov.: 32 AF XY: 0.306 AC XY: 22729AN XY: 74218
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fanconi anemia complementation group I Benign:3
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 specified Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 08, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Fanconi anemia Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;T;T;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T;T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;.;.;M;.
MutationTaster
Benign
P;P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N;D;D;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
P;B;.;.;.;.;.
Vest4
MPC
0.019
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 31
Find out detailed SpliceAI scores and Pangolin per-transcript scores at