15-89247480-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001113378.2(FANCI):c.-19-149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0735 in 646,390 control chromosomes in the GnomAD database, including 2,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.094 (871 hom., cov: 31)
  • Exomes 𝑓: 0.067 (1252 hom.)
• Consequence: FANCI NM_001113378.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.00

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-89247480-A-G is Benign according to our data. Variant chr15-89247480-A-G is described in ClinVar as [Benign]. Clinvar id is 1243727.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCI	NM_001113378.2	c.-19-149A>G		intron_variant		ENST00000310775.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCI	ENST00000310775.12	c.-19-149A>G		intron_variant		1	NM_001113378.2	P1

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14249 AN: 152134 Hom.: 866 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0826

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0713

Gnomad OTH AF: 0.0881

GnomAD4 exome AF: 0.0673 AC: 33257 AN: 494138 Hom.: 1252 AF XY: 0.0674 AC XY: 17798 AN XY: 263988

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.0491

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.000154

Gnomad4 SAS exome AF: 0.0772

Gnomad4 FIN exome AF: 0.0354

Gnomad4 NFE exome AF: 0.0709

Gnomad4 OTH exome AF: 0.0740

GnomAD4 genome AF: 0.0937 AC: 14263 AN: 152252 Hom.: 871 Cov.: 31 AF XY: 0.0914 AC XY: 6802 AN XY: 74450

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.0632

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0813

Gnomad4 FIN AF: 0.0299

Gnomad4 NFE AF: 0.0713

Gnomad4 OTH AF: 0.0872

Alfa AF: 0.0823 Hom.: 128

Bravo AF: 0.0986

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.8
Dann	Benign	0.78

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

Other links and lift over

dbSNP: rs73475356; hg19: chr15-89790711;