Submissions for variant NM_001113378.2(FANCI):c.3865A>G (p.Ile1289Val)

gnomAD frequency: 0.00150  dbSNP: rs114549781

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000547520	SCV000626315	benign	Fanconi anemia	2024-12-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001194160	SCV001363470	benign	not specified	2019-12-12	criteria provided, single submitter	clinical testing	Variant summary: FANCI c.3865A>G (p.Ile1289Val) results in a conservative amino acid change located in the FANCI solenoid 4 domain (IPR029314) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00035 in 251470 control chromosomes, predominantly at a frequency of 0.004 within the African or African-American subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 14 fold of the estimated maximal expected allele frequency for a pathogenic variant in FANCI causing Fanconi anemia phenotype (0.00028), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.3865A>G in individuals affected with Fanconi anemia, complementation group I and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Sema4, Sema4	RCV000547520	SCV002529851	likely benign	Fanconi anemia	2021-06-30	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV003403255	SCV004137611	likely benign	not provided	2022-10-01	criteria provided, single submitter	clinical testing	FANCI: BS2
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV005235380	SCV005880737	benign	Fanconi anemia complementation group I	2025-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003979941	SCV004789526	likely benign	FANCI-related disorder	2020-10-28	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).