15-89293908-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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	Q9NVI1-3

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		Q9NVI1-3

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

GnomAD3 exomes

AF:

0.0247

AC:

6222

AN:

251430

Hom.:

508

AF XY:

0.0198

AC XY:

2685

AN XY:

135888

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 SAS exome

AF:

0.00679

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

Gnomad4 AFR exome

AF:

0.244

Gnomad4 AMR exome

AF:

0.0222

Gnomad4 ASJ exome

AF:

0.00383

Gnomad4 EAS exome

AF:

0.0145

Gnomad4 SAS exome

AF:

0.00681

Gnomad4 FIN exome

AF:

0.0240

Gnomad4 NFE exome

AF:

0.00230

Gnomad4 OTH exome

AF:

0.0238

GnomAD4 genome

AF:

0.0736

AC:

11195

AN:

152076

Hom.:

1201

Cov.:

AF XY:

0.0713

AC XY:

5305

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.238

Gnomad4 AMR

AF:

0.0421

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.0149

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.0225

Gnomad4 NFE

AF:

0.00325

Gnomad4 OTH

AF:

0.0597

Alfa

AF:

0.0324

Hom.:

293

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

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. -

Oct 17, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

DANN

Benign

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over