15-89293908-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001113378.2(FANCI):c.2367G>T(p.Ala789Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,613,882 control chromosomes in the GnomAD database, including 2,370 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.074 ( 1201 hom., cov: 32)

Exomes 𝑓: 0.011 ( 1169 hom. )

Consequence

FANCI
NM_001113378.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.257

Publications

7 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 15-89293908-G-T is Benign according to our data. Variant chr15-89293908-G-T is described in ClinVar as Benign. ClinVar VariationId is 257483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.257 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCI	NM_001113378.2 link	c.2367G>T	p.Ala789Ala	synonymous_variant	Exon 23 of 38	ENST00000310775.12	NP_001106849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCI	ENST00000310775.12 link	c.2367G>T	p.Ala789Ala	synonymous_variant	Exon 23 of 38	1	NM_001113378.2	ENSP00000310842.8

Frequencies

GnomAD3 genomes

AF:

0.0735

AC:

11167

AN:

151960

Hom.:

1199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0422

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.0148

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.0225

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.00325

Gnomad OTH

AF:

0.0603

GnomAD2 exomes

AF:

0.0247

AC:

6222

AN:

251430

AF XY:

0.0198

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.0202

Gnomad ASJ exome

AF:

0.00417

Gnomad EAS exome

AF:

0.0137

Gnomad FIN exome

AF:

0.0238

Gnomad NFE exome

AF:

0.00353

Gnomad OTH exome

AF:

0.0220

GnomAD4 exome

AF:

0.0109

AC:

16002

AN:

1461806

Hom.:

1169

Cov.:

AF XY:

0.0102

AC XY:

7403

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.244

AC:

8178

AN:

33470

American (AMR)

AF:

0.0222

AC:

992

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00383

AC:

100

AN:

26132

East Asian (EAS)

AF:

0.0145

AC:

575

AN:

39676

South Asian (SAS)

AF:

0.00681

AC:

587

AN:

86256

European-Finnish (FIN)

AF:

0.0240

AC:

1282

AN:

53414

Middle Eastern (MID)

AF:

0.0496

AC:

286

AN:

5768

European-Non Finnish (NFE)

AF:

0.00230

AC:

2562

AN:

1111976

Other (OTH)

AF:

0.0238

AC:

1440

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

725

1449

2174

2898

3623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.0736

AC:

11195

AN:

152076

Hom.:

1201

Cov.:

AF XY:

0.0713

AC XY:

5305

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.238

AC:

9840

AN:

41426

American (AMR)

AF:

0.0421

AC:

644

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.0149

AC:

AN:

5176

South Asian (SAS)

AF:

0.00539

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0225

AC:

238

AN:

10582

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00325

AC:

221

AN:

68002

Other (OTH)

AF:

0.0597

AC:

126

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

453

906

1358

1811

2264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0342

Hom.:

399

Bravo

AF:

0.0839

Asia WGS

AF:

0.0300

AC:

104

AN:

3478

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

Oct 17, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

not provided

Benign:2

Mar 01, 2019

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 03, 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

-0.41

CADD

Benign

4.9

(source)

DANN

Benign

0.56

PhyloP100

0.26

Mutation Taster

=97/3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over