rs1981623

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+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,588,096 control chromosomes in the GnomAD database, including 115,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10607 hom., cov: 32)

Exomes 𝑓: 0.38 ( 104814 hom. )

Consequence

FANCI
NM_001113378.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.35

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: 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=-0.67).

BP6

Variant 15-89263479-C-T is Benign according to our data. Variant chr15-89263479-C-T is described in ClinVar as Benign. ClinVar VariationId is 257490.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCI	NM_001113378.2 link	c.545+19C>T		intron_variant	Intron 7 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.545+19C>T		intron_variant	Intron 7 of 37	1	NM_001113378.2	ENSP00000310842.8		Q9NVI1-3

Frequencies

GnomAD3 genomes

AF:

0.372

AC:

56394

AN:

151792

Hom.:

10602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.469

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.369

GnomAD2 exomes

AF:

0.381

AC:

95568

AN:

250536

AF XY:

0.384

show subpopulations

Gnomad AFR exome

AF:

0.328

Gnomad AMR exome

AF:

0.382

Gnomad ASJ exome

AF:

0.382

Gnomad EAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.460

Gnomad NFE exome

AF:

0.383

Gnomad OTH exome

AF:

0.381

GnomAD4 exome

AF:

0.378

AC:

542995

AN:

1436186

Hom.:

104814

Cov.:

AF XY:

0.379

AC XY:

271469

AN XY:

715748

show subpopulations

African (AFR)

AF:

0.321

AC:

10606

AN:

33058

American (AMR)

AF:

0.378

AC:

16832

AN:

44556

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

9936

AN:

25926

East Asian (EAS)

AF:

0.309

AC:

12198

AN:

39506

South Asian (SAS)

AF:

0.384

AC:

32894

AN:

85612

European-Finnish (FIN)

AF:

0.454

AC:

24097

AN:

53122

Middle Eastern (MID)

AF:

0.365

AC:

2085

AN:

5718

European-Non Finnish (NFE)

AF:

0.378

AC:

411618

AN:

1089132

Other (OTH)

AF:

0.382

AC:

22729

AN:

59556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.410

Heterozygous variant carriers

15781

31561

47342

63122

78903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12706

25412

38118

50824

63530

<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:

56425

AN:

151910

Hom.:

10607

Cov.:

AF XY:

0.376

AC XY:

27898

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.330

AC:

13665

AN:

41422

American (AMR)

AF:

0.351

AC:

5366

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.370

AC:

1278

AN:

3454

East Asian (EAS)

AF:

0.324

AC:

1667

AN:

5152

South Asian (SAS)

AF:

0.378

AC:

1818

AN:

4808

European-Finnish (FIN)

AF:

0.469

AC:

4943

AN:

10534

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.389

AC:

26459

AN:

67934

Other (OTH)

AF:

0.366

AC:

775

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1833

3667

5500

7334

9167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.388

Hom.:

2196

Bravo

AF:

0.365

Asia WGS

AF:

0.350

AC:

1216

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group I

Benign:3

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

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

-0.67

CADD

Benign

1.6

(source)

DANN

Benign

0.75

PhyloP100

-1.4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over