NM_001113378.2:c.288+37G>A

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.288+37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,606,636 control chromosomes in the GnomAD database, including 133,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17674 hom., cov: 31)

Exomes 𝑓: 0.39 ( 115633 hom. )

Consequence

FANCI
NM_001113378.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.236

Publications

14 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:

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=-0.91).

BP6

Variant 15-89260880-G-A is Benign according to our data. Variant chr15-89260880-G-A is described in ClinVar as Benign. ClinVar VariationId is 257486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 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.288+37G>A	intron	N/A	NP_001106849.1	Q9NVI1-3
FANCI	NM_001376911.1		c.288+37G>A	intron	N/A	NP_001363840.1	Q9NVI1-3
FANCI	NM_018193.3		c.288+37G>A	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.288+37G>A	intron	N/A	ENSP00000310842.8	Q9NVI1-3
FANCI	ENST00000567996.5	TSL:1	c.288+37G>A	intron	N/A	ENSP00000458024.1	Q9NVI1-4
FANCI	ENST00000674831.1		c.288+37G>A	intron	N/A	ENSP00000502474.1	A0A6Q8PH09

Frequencies

GnomAD3 genomes

AF:

0.468

AC:

70962

AN:

151776

Hom.:

17647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.651

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.377

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.492

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.393

Gnomad OTH

AF:

0.435

GnomAD2 exomes

AF:

0.411

AC:

103140

AN:

250888

AF XY:

0.408

show subpopulations

Gnomad AFR exome

AF:

0.650

Gnomad AMR exome

AF:

0.401

Gnomad ASJ exome

AF:

0.390

Gnomad EAS exome

AF:

0.339

Gnomad FIN exome

AF:

0.484

Gnomad NFE exome

AF:

0.386

Gnomad OTH exome

AF:

0.398

GnomAD4 exome

AF:

0.394

AC:

573701

AN:

1454742

Hom.:

115633

Cov.:

AF XY:

0.394

AC XY:

285051

AN XY:

723768

show subpopulations

African (AFR)

AF:

0.657

AC:

21938

AN:

33368

American (AMR)

AF:

0.398

AC:

17754

AN:

44584

Ashkenazi Jewish (ASJ)

AF:

0.391

AC:

10159

AN:

25960

East Asian (EAS)

AF:

0.324

AC:

12767

AN:

39352

South Asian (SAS)

AF:

0.391

AC:

33602

AN:

85958

European-Finnish (FIN)

AF:

0.477

AC:

25218

AN:

52834

Middle Eastern (MID)

AF:

0.399

AC:

2283

AN:

5720

European-Non Finnish (NFE)

AF:

0.384

AC:

425431

AN:

1106966

Other (OTH)

AF:

0.409

AC:

24549

AN:

60000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

17869

35738

53608

71477

89346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13402

26804

40206

53608

67010

<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:

0.468

AC:

71030

AN:

151894

Hom.:

17674

Cov.:

AF XY:

0.470

AC XY:

34899

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.651

AC:

26978

AN:

41428

American (AMR)

AF:

0.389

AC:

5938

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

1308

AN:

3468

East Asian (EAS)

AF:

0.338

AC:

1743

AN:

5160

South Asian (SAS)

AF:

0.384

AC:

1851

AN:

4826

European-Finnish (FIN)

AF:

0.492

AC:

5172

AN:

10518

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.393

AC:

26665

AN:

67904

Other (OTH)

AF:

0.431

AC:

909

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1828

3656

5485

7313

9141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.413

Hom.:

35528

Bravo

AF:

0.472

Asia WGS

AF:

0.370

AC:

1287

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 (2)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.21

(source)

DANN

Benign

0.38

PhyloP100

-0.24

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