chr15-89301343-A-C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001113378.2(FANCI):​c.2907A>C​(p.Leu969Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L969S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

FANCI
NM_001113378.2 missense

Scores

4
15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.22

Publications

2 publications found
Variant links:
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 I
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
  • Fanconi anemia
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.010856152).
BP6
Variant 15-89301343-A-C is Benign according to our data. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-89301343-A-C is described in CliVar as Likely_benign. Clinvar id is 456213.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FANCINM_001113378.2 linkc.2907A>C p.Leu969Phe missense_variant Exon 27 of 38 ENST00000310775.12 NP_001106849.1 Q9NVI1-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FANCIENST00000310775.12 linkc.2907A>C p.Leu969Phe missense_variant Exon 27 of 38 1 NM_001113378.2 ENSP00000310842.8 Q9NVI1-3

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152150
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00135
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000203
AC:
51
AN:
251474
AF XY:
0.000177
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00277
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000390
AC:
57
AN:
1461292
Hom.:
0
Cov.:
31
AF XY:
0.0000371
AC XY:
27
AN XY:
727006
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33462
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26126
East Asian (EAS)
AF:
0.00134
AC:
53
AN:
39686
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86250
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111488
Other (OTH)
AF:
0.0000497
AC:
3
AN:
60368
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
4
9
13
18
22
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152268
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74464
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41558
American (AMR)
AF:
0.00
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00135
AC:
7
AN:
5186
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68016
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.454
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000522
Hom.:
0
Bravo
AF:
0.000117
ExAC
AF:
0.000239
AC:
29

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Fanconi anemia Benign:1
Dec 22, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.049
.;T
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.42
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.011
T;T
MetaSVM
Benign
-0.70
T
MutationAssessor
Uncertain
2.4
.;M
PhyloP100
1.2
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.92
N;N
REVEL
Benign
0.16
Sift
Benign
0.28
T;T
Sift4G
Benign
0.17
T;T
Polyphen
0.91
P;P
Vest4
0.24
MutPred
0.20
.;Gain of MoRF binding (P = 0.1612);
MVP
0.65
MPC
0.017
ClinPred
0.075
T
GERP RS
-3.0
Varity_R
0.084
gMVP
0.13
Mutation Taster
=88/12
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.20
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.20
Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs568094959; hg19: chr15-89844574; API