rs2159081

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.3006+15A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,526,138 control chromosomes in the GnomAD database, including 116,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11086 hom., cov: 32)

Exomes 𝑓: 0.39 ( 105565 hom. )

Consequence

FANCI
NM_001113378.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.08

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:

LOC124903548 (HGNC:):

LOC124903548 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 (BayesDel_noAF=-0.92).

BP6

Variant 15-89301457-A-C is Benign according to our data. Variant chr15-89301457-A-C is described in ClinVar as [Benign]. Clinvar id is 257487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCI	NM_001113378.2 link	c.3006+15A>C		intron_variant	Intron 27 of 37	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.3006+15A>C		intron_variant	Intron 27 of 37	1	NM_001113378.2	ENSP00000310842.8		Q9NVI1-3

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57561

AN:

151882

Hom.:

11070

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.377

Gnomad EAS

AF:

0.375

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.493

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.368

GnomAD3 exomes

AF:

0.393

AC:

98913

AN:

251464

Hom.:

19817

AF XY:

0.397

AC XY:

53942

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.327

Gnomad AMR exome

AF:

0.382

Gnomad ASJ exome

AF:

0.389

Gnomad EAS exome

AF:

0.382

Gnomad SAS exome

AF:

0.403

Gnomad FIN exome

AF:

0.485

Gnomad NFE exome

AF:

0.389

Gnomad OTH exome

AF:

0.386

GnomAD4 exome

AF:

0.391

AC:

537004

AN:

1374138

Hom.:

105565

Cov.:

AF XY:

0.392

AC XY:

269901

AN XY:

688942

show subpopulations

Gnomad4 AFR exome

AF:

0.335

Gnomad4 AMR exome

AF:

0.377

Gnomad4 ASJ exome

AF:

0.392

Gnomad4 EAS exome

AF:

0.355

Gnomad4 SAS exome

AF:

0.405

Gnomad4 FIN exome

AF:

0.479

Gnomad4 NFE exome

AF:

0.389

Gnomad4 OTH exome

AF:

0.391

GnomAD4 genome

AF:

0.379

AC:

57607

AN:

152000

Hom.:

11086

Cov.:

AF XY:

0.386

AC XY:

28695

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.336

Gnomad4 AMR

AF:

0.348

Gnomad4 ASJ

AF:

0.377

Gnomad4 EAS

AF:

0.376

Gnomad4 SAS

AF:

0.397

Gnomad4 FIN

AF:

0.493

Gnomad4 NFE

AF:

0.394

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.390

Hom.:

2611

Bravo

AF:

0.368

Asia WGS

AF:

0.367

AC:

1275

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

- -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

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

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.47

DANN

Benign

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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