NM_001113378.2:c.545+30G>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.545+30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,561,272 control chromosomes in the GnomAD database, including 110,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10604 hom., cov: 32)

Exomes 𝑓: 0.37 ( 99805 hom. )

Consequence

FANCI
NM_001113378.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.38

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=-0.89).

BP6

Variant 15-89263490-G-A is Benign according to our data. Variant chr15-89263490-G-A is described in ClinVar as Benign. ClinVar VariationId is 257491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 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.545+30G>A	intron	N/A	NP_001106849.1	Q9NVI1-3
FANCI	NM_001376911.1		c.545+30G>A	intron	N/A	NP_001363840.1	Q9NVI1-3
FANCI	NM_018193.3		c.545+30G>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.545+30G>A	intron	N/A	ENSP00000310842.8	Q9NVI1-3
FANCI	ENST00000567996.5	TSL:1	c.545+30G>A	intron	N/A	ENSP00000458024.1	Q9NVI1-4
FANCI	ENST00000674831.1		c.545+30G>A	intron	N/A	ENSP00000502474.1	A0A6Q8PH09

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56363

AN:

151792

Hom.:

10599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.470

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.368

GnomAD2 exomes

AF:

0.381

AC:

95314

AN:

250266

AF XY:

0.384

show subpopulations

Gnomad AFR exome

AF:

0.326

Gnomad AMR exome

AF:

0.381

Gnomad ASJ exome

AF:

0.381

Gnomad EAS exome

AF:

0.323

Gnomad FIN exome

AF:

0.459

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.380

GnomAD4 exome

AF:

0.373

AC:

525288

AN:

1409362

Hom.:

99805

Cov.:

AF XY:

0.375

AC XY:

263690

AN XY:

704002

show subpopulations

African (AFR)

AF:

0.316

AC:

10321

AN:

32666

American (AMR)

AF:

0.377

AC:

16790

AN:

44528

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

9831

AN:

25786

East Asian (EAS)

AF:

0.308

AC:

12115

AN:

39368

South Asian (SAS)

AF:

0.382

AC:

32488

AN:

85012

European-Finnish (FIN)

AF:

0.453

AC:

24044

AN:

53044

Middle Eastern (MID)

AF:

0.361

AC:

2047

AN:

5674

European-Non Finnish (NFE)

AF:

0.372

AC:

395540

AN:

1064646

Other (OTH)

AF:

0.377

AC:

22112

AN:

58638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.403

Heterozygous variant carriers

14828

29655

44483

59310

74138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12078

24156

36234

48312

60390

<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:

0.371

AC:

56394

AN:

151910

Hom.:

10604

Cov.:

AF XY:

0.376

AC XY:

27887

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.329

AC:

13624

AN:

41410

American (AMR)

AF:

0.351

AC:

5364

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1284

AN:

3464

East Asian (EAS)

AF:

0.323

AC:

1668

AN:

5168

South Asian (SAS)

AF:

0.377

AC:

1815

AN:

4810

European-Finnish (FIN)

AF:

0.470

AC:

4953

AN:

10540

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.389

AC:

26458

AN:

67934

Other (OTH)

AF:

0.366

AC:

772

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1840

3681

5521

7362

9202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<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:

0.386

Hom.:

3053

Bravo

AF:

0.365

Asia WGS

AF:

0.351

AC:

1217

AN:

3474

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

-0.89

CADD

Benign

0.012

(source)

DANN

Benign

0.62

PhyloP100

-3.4

PromoterAI

-0.0034

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over