NM_001113378.2:c.2907A>C

Variant names:

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

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

FANCI links:

LOC124903548 (HGNC:):

LOC124903548 links:

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
FANCI	NM_001113378.2 link	c.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
FANCI	ENST00000310775.12 link	c.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:

AN:

152150

Hom.:

Cov.:

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:

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:

AN:

1461292

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727006

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00134

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111488

Other (OTH)

AF:

0.0000497

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

AN:

152268

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41558

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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.:

Bravo

AF:

0.000117

ExAC

AF:

0.000239

AC:

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

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.048

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.4

.;M

PhyloP100

1.2

PrimateAI

Benign

0.41

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

GERP RS

-3.0

Varity_R

0.084

gMVP

0.13

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over