rs2159081

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.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

Publications

15 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: Labcorp Genetics (formerly Invitae), ClinGen, 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: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113378.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FANCI	NM_001113378.2	MANE Select	c.3006+15A>C	intron	N/A	NP_001106849.1	Q9NVI1-3
FANCI	NM_001376911.1		c.3006+15A>C	intron	N/A	NP_001363840.1	Q9NVI1-3
FANCI	NM_018193.3		c.2826+15A>C	intron	N/A	NP_060663.2	Q9NVI1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FANCI	ENST00000310775.12	TSL:1 MANE Select	c.3006+15A>C	intron	N/A	ENSP00000310842.8	Q9NVI1-3
FANCI	ENST00000674831.1		c.3006+15A>C	intron	N/A	ENSP00000502474.1	A0A6Q8PH09
FANCI	ENST00000940814.1		c.3030+15A>C	intron	N/A	ENSP00000610873.1

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

GnomAD2 exomes

AF:

0.393

AC:

98913

AN:

251464

AF XY:

0.397

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 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

African (AFR)

AF:

0.335

AC:

10648

AN:

31778

American (AMR)

AF:

0.377

AC:

16808

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

10041

AN:

25606

East Asian (EAS)

AF:

0.355

AC:

13951

AN:

39272

South Asian (SAS)

AF:

0.405

AC:

34262

AN:

84624

European-Finnish (FIN)

AF:

0.479

AC:

25564

AN:

53366

Middle Eastern (MID)

AF:

0.372

AC:

2088

AN:

5614

European-Non Finnish (NFE)

AF:

0.389

AC:

401208

AN:

1031836

Other (OTH)

AF:

0.391

AC:

22434

AN:

57424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

14796

29592

44388

59184

73980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12156

24312

36468

48624

60780

<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:

0.379

AC:

57607

AN:

152000

Hom.:

11086

Cov.:

AF XY:

0.386

AC XY:

28695

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.336

AC:

13930

AN:

41464

American (AMR)

AF:

0.348

AC:

5320

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

1307

AN:

3470

East Asian (EAS)

AF:

0.376

AC:

1939

AN:

5160

South Asian (SAS)

AF:

0.397

AC:

1914

AN:

4816

European-Finnish (FIN)

AF:

0.493

AC:

5198

AN:

10552

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.394

AC:

26775

AN:

67954

Other (OTH)

AF:

0.365

AC:

770

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1875

3750

5626

7501

9376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<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:

0.376

Hom.:

6631

Bravo

AF:

0.368

Asia WGS

AF:

0.367

AC:

1275

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Fanconi anemia complementation group I (4)

not provided (2)

Fanconi anemia (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.47

(source)

DANN

Benign

0.38

PhyloP100

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over