chr15-89316836-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001113378.2(FANCI):c.*377T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,607,264 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001113378.2 3_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FANCI | ENST00000310775.12 | c.*377T>C | 3_prime_UTR_variant | Exon 38 of 38 | 1 | NM_001113378.2 | ENSP00000310842.8 | |||
POLG | ENST00000268124.11 | c.3644-9A>G | intron_variant | Intron 22 of 22 | 1 | NM_002693.3 | ENSP00000268124.5 |
Frequencies
GnomAD3 genomes AF: 0.00724 AC: 1101AN: 152162Hom.: 16 Cov.: 32
GnomAD3 exomes AF: 0.00179 AC: 449AN: 251238Hom.: 6 AF XY: 0.00124 AC XY: 168AN XY: 135824
GnomAD4 exome AF: 0.000735 AC: 1069AN: 1454984Hom.: 15 Cov.: 29 AF XY: 0.000628 AC XY: 455AN XY: 724412
GnomAD4 genome AF: 0.00725 AC: 1104AN: 152280Hom.: 16 Cov.: 32 AF XY: 0.00729 AC XY: 543AN XY: 74472
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Progressive sclerosing poliodystrophy Benign:2
The NM_002693.2:c.3644-9A>G (NP_002684.1:p.=) [GRCH38: NC_000015.10:g.89316836T>C] variant in FANCI gene is interpretated to be a Benign based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. BA1:Minor allele frequency is too high for the Mitochondrial DNA depletion syndrome 4A (Alpers type). BP4:Computational evidence/predictors indicate no impact on the FANCI structure, function, or protein-protein interaction. Based on the evidence criteria codes applied, the variant is suggested to be Benign. -
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not provided Benign:1
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Fanconi anemia complementation group I Benign:1
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at