Variant rs1981623 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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:5

Conservation

PhyloP100: -1.35

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
FANCI	NM_001113378.2 linkuse as main transcript	c.545+19C>T		intron_variant		ENST00000310775.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCI	ENST00000310775.12 linkuse as main transcript	c.545+19C>T		intron_variant		1	NM_001113378.2	P1	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

GnomAD3 exomes

AF:

0.381

AC:

95568

AN:

250536

Hom.:

18617

AF XY:

0.384

AC XY:

52074

AN XY:

135452

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 SAS exome

AF:

0.384

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

Gnomad4 AFR exome

AF:

0.321

Gnomad4 AMR exome

AF:

0.378

Gnomad4 ASJ exome

AF:

0.383

Gnomad4 EAS exome

AF:

0.309

Gnomad4 SAS exome

AF:

0.384

Gnomad4 FIN exome

AF:

0.454

Gnomad4 NFE exome

AF:

0.378

Gnomad4 OTH exome

AF:

0.382

GnomAD4 genome

AF:

0.371

AC:

56425

AN:

151910

Hom.:

10607

Cov.:

AF XY:

0.376

AC XY:

27898

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.330

Gnomad4 AMR

AF:

0.351

Gnomad4 ASJ

AF:

0.370

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.378

Gnomad4 FIN

AF:

0.469

Gnomad4 NFE

AF:

0.389

Gnomad4 OTH

AF:

0.366

Alfa

AF:

0.389

Hom.:

2145

Bravo

AF:

0.365

Asia WGS

AF:

0.350

AC:

1216

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group I

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Fanconi anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

Cadd

Benign

1.6

Dann

Benign

0.75

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