rs62020347

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.164C>T(p.Pro55Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0588 in 1,613,550 control chromosomes in the GnomAD database, including 3,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 222 hom., cov: 32)

Exomes 𝑓: 0.060 ( 2889 hom. )

Consequence

FANCI
NM_001113378.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 6.63

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=0.0022953153).

BP6

Variant 15-89260719-C-T is Benign according to our data. Variant chr15-89260719-C-T is described in ClinVar as [Benign]. Clinvar id is 257480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCI	NM_001113378.2 link	c.164C>T	p.Pro55Leu	missense_variant	Exon 4 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.164C>T	p.Pro55Leu	missense_variant	Exon 4 of 38	1	NM_001113378.2	ENSP00000310842.8		Q9NVI1-3

Frequencies

GnomAD3 genomes

AF:

0.0470

AC:

7152

AN:

152070

Hom.:

223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.0451

Gnomad ASJ

AF:

0.0896

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0803

Gnomad FIN

AF:

0.0232

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0646

Gnomad OTH

AF:

0.0536

GnomAD3 exomes

AF:

0.0527

AC:

13246

AN:

251442

Hom.:

468

AF XY:

0.0559

AC XY:

7603

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0234

Gnomad AMR exome

AF:

0.0329

Gnomad ASJ exome

AF:

0.0867

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.0757

Gnomad FIN exome

AF:

0.0264

Gnomad NFE exome

AF:

0.0667

Gnomad OTH exome

AF:

0.0593

GnomAD4 exome

AF:

0.0600

AC:

87652

AN:

1461362

Hom.:

2889

Cov.:

AF XY:

0.0608

AC XY:

44173

AN XY:

727026

show subpopulations

Gnomad4 AFR exome

AF:

0.0200

Gnomad4 AMR exome

AF:

0.0347

Gnomad4 ASJ exome

AF:

0.0891

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.0745

Gnomad4 FIN exome

AF:

0.0273

Gnomad4 NFE exome

AF:

0.0643

Gnomad4 OTH exome

AF:

0.0556

GnomAD4 genome

AF:

0.0469

AC:

7145

AN:

152188

Hom.:

222

Cov.:

AF XY:

0.0459

AC XY:

3414

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0214

Gnomad4 AMR

AF:

0.0450

Gnomad4 ASJ

AF:

0.0896

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.0789

Gnomad4 FIN

AF:

0.0232

Gnomad4 NFE

AF:

0.0646

Gnomad4 OTH

AF:

0.0530

Alfa

AF:

0.0622

Hom.:

499

Bravo

AF:

0.0467

TwinsUK

AF:

0.0677

AC:

251

ALSPAC

AF:

0.0654

AC:

252

ESP6500AA

AF:

0.0234

AC:

103

ESP6500EA

AF:

0.0678

AC:

583

ExAC

AF:

0.0546

AC:

6628

Asia WGS

AF:

0.0450

AC:

157

AN:

3478

EpiCase

AF:

0.0683

EpiControl

AF:

0.0656

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group I

Benign:3

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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. -

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

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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 03, 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

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

.;T;T;T;T;.;T

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.87

D;D;D;D;D;D;D

MetaRNN

Benign

0.0023

T;T;T;T;T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.8

M;M;.;.;.;M;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.1

N;D;D;D;D;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0040

D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D

Polyphen

1.0

D;D;.;.;.;.;.

Vest4

0.78

MPC

0.088

ClinPred

0.015

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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