NM_001113378.2:c.2629A>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001113378.2(FANCI):c.2629A>T(p.Ile877Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0967 in 1,551,466 control chromosomes in the GnomAD database, including 7,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.074 ( 561 hom., cov: 32)

Exomes 𝑓: 0.099 ( 7261 hom. )

Consequence

FANCI
NM_001113378.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 4.84

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016543865).

BP6

Variant 15-89295087-A-T is Benign according to our data. Variant chr15-89295087-A-T is described in ClinVar as [Benign]. Clinvar id is 257485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCI	NM_001113378.2 link	c.2629A>T	p.Ile877Leu	missense_variant	Exon 24 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.2629A>T	p.Ile877Leu	missense_variant	Exon 24 of 38	1	NM_001113378.2	ENSP00000310842.8		Q9NVI1-3

Frequencies

GnomAD3 genomes

AF:

0.0739

AC:

11252

AN:

152182

Hom.:

561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0179

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0705

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.0581

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.0934

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.0746

GnomAD3 exomes

AF:

0.0883

AC:

13805

AN:

156354

Hom.:

685

AF XY:

0.0911

AC XY:

7551

AN XY:

82852

show subpopulations

Gnomad AFR exome

AF:

0.0123

Gnomad AMR exome

AF:

0.0713

Gnomad ASJ exome

AF:

0.0972

Gnomad EAS exome

AF:

0.0452

Gnomad SAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.0986

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.0961

GnomAD4 exome

AF:

0.0992

AC:

138754

AN:

1399166

Hom.:

7261

Cov.:

AF XY:

0.0997

AC XY:

68832

AN XY:

690094

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.0708

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.0723

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.0963

Gnomad4 NFE exome

AF:

0.103

Gnomad4 OTH exome

AF:

0.0933

GnomAD4 genome

AF:

0.0739

AC:

11251

AN:

152300

Hom.:

561

Cov.:

AF XY:

0.0737

AC XY:

5492

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0179

Gnomad4 AMR

AF:

0.0704

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.0581

Gnomad4 SAS

AF:

0.105

Gnomad4 FIN

AF:

0.0934

Gnomad4 NFE

AF:

0.103

Gnomad4 OTH

AF:

0.0743

Alfa

AF:

0.101

Hom.:

602

Bravo

AF:

0.0685

TwinsUK

AF:

0.0968

AC:

359

ALSPAC

AF:

0.0856

AC:

330

ESP6500AA

AF:

0.0210

AC:

ESP6500EA

AF:

0.110

AC:

349

ExAC

AF:

0.0880

AC:

2196

Asia WGS

AF:

0.104

AC:

361

AN:

3478

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:4

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Nov 15, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fanconi anemia

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.085

Eigen

Benign

-0.029

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.87

REVEL

Benign

0.13

Sift

Benign

0.19

Sift4G

Benign

0.14

Polyphen

0.072

Vest4

0.13

MutPred

0.34

Loss of MoRF binding (P = 0.1504);

MPC

0.016

ClinPred

0.017

GERP RS

6.0

Varity_R

0.11

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over