rs17803620
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_001113378.2(FANCI):c.257C>A(p.Ala86Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,872 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A86V) has been classified as Benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
FANCI
NM_001113378.2 missense
NM_001113378.2 missense
Scores
1
11
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.06
Publications
51 publications found
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]
FANCI Gene-Disease associations (from GenCC):
- Fanconi anemia complementation group IInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
- Fanconi anemiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 151872Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151872
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1AN: 1461570Hom.: 0 Cov.: 39 AF XY: 0.00000138 AC XY: 1AN XY: 727114 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1461570
Hom.:
Cov.:
39
AF XY:
AC XY:
1
AN XY:
727114
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33470
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26130
East Asian (EAS)
AF:
AC:
0
AN:
39682
South Asian (SAS)
AF:
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
AC:
0
AN:
53372
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111794
Other (OTH)
AF:
AC:
1
AN:
60384
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000658 AC: 1AN: 151872Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74136 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151872
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74136
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41354
American (AMR)
AF:
AC:
0
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5176
South Asian (SAS)
AF:
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
AC:
0
AN:
10528
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67946
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;T;T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;.;.;M;.
PhyloP100
PrimateAI
Benign
T
PROVEAN
Benign
N;N;D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D
Polyphen
D;D;.;.;.;.;.
Vest4
MutPred
Gain of disorder (P = 0.0204);Gain of disorder (P = 0.0204);Gain of disorder (P = 0.0204);Gain of disorder (P = 0.0204);Gain of disorder (P = 0.0204);Gain of disorder (P = 0.0204);Gain of disorder (P = 0.0204);
MVP
MPC
0.10
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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