NM_001113378.2:c.1698+15C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001113378.2(FANCI):c.1698+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,612,664 control chromosomes in the GnomAD database, including 133,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17029 hom., cov: 32)

Exomes 𝑓: 0.40 ( 116724 hom. )

Consequence

FANCI
NM_001113378.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.834

Publications

12 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 15-89283265-C-T is Benign according to our data. Variant chr15-89283265-C-T is described in ClinVar as Benign. ClinVar VariationId is 257481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCI	NM_001113378.2 link	c.1698+15C>T		intron_variant	Intron 17 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.1698+15C>T		intron_variant	Intron 17 of 37	1	NM_001113378.2	ENSP00000310842.8		Q9NVI1-3

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

70053

AN:

151920

Hom.:

17005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.623

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.492

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.433

GnomAD2 exomes

AF:

0.412

AC:

103562

AN:

251368

AF XY:

0.410

show subpopulations

Gnomad AFR exome

AF:

0.622

Gnomad AMR exome

AF:

0.402

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.340

Gnomad FIN exome

AF:

0.486

Gnomad NFE exome

AF:

0.389

Gnomad OTH exome

AF:

0.401

GnomAD4 exome

AF:

0.397

AC:

579169

AN:

1460624

Hom.:

116724

Cov.:

AF XY:

0.396

AC XY:

288026

AN XY:

726666

show subpopulations

African (AFR)

AF:

0.630

AC:

21088

AN:

33448

American (AMR)

AF:

0.399

AC:

17852

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

9812

AN:

26120

East Asian (EAS)

AF:

0.326

AC:

12935

AN:

39670

South Asian (SAS)

AF:

0.404

AC:

34813

AN:

86238

European-Finnish (FIN)

AF:

0.479

AC:

25510

AN:

53240

Middle Eastern (MID)

AF:

0.399

AC:

2301

AN:

5762

European-Non Finnish (NFE)

AF:

0.387

AC:

430187

AN:

1111086

Other (OTH)

AF:

0.409

AC:

24671

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

16820

33640

50459

67279

84099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13498

26996

40494

53992

67490

<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:

0.461

AC:

70117

AN:

152040

Hom.:

17029

Cov.:

AF XY:

0.465

AC XY:

34532

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.623

AC:

25845

AN:

41482

American (AMR)

AF:

0.388

AC:

5933

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1265

AN:

3468

East Asian (EAS)

AF:

0.338

AC:

1750

AN:

5174

South Asian (SAS)

AF:

0.396

AC:

1909

AN:

4826

European-Finnish (FIN)

AF:

0.492

AC:

5187

AN:

10536

Middle Eastern (MID)

AF:

0.377

AC:

110

AN:

292

European-Non Finnish (NFE)

AF:

0.395

AC:

26856

AN:

67956

Other (OTH)

AF:

0.430

AC:

907

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1879

3759

5638

7518

9397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<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:

0.429

Hom.:

2673

Bravo

AF:

0.464

Asia WGS

AF:

0.378

AC:

1312

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

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

- -

Aug 10, 2021

Genome-Nilou Lab

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

- -

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 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

-0.87

CADD

Benign

2.1

(source)

DANN

Benign

0.62

PhyloP100

-0.83

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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