rs540371794
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001113378.2(FANCI):c.*560A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 609,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 0 hom. )
Consequence
FANCI
NM_001113378.2 3_prime_UTR
NM_001113378.2 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0860
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]
POLG (HGNC:9179): (DNA polymerase gamma, catalytic subunit) Mitochondrial DNA polymerase is heterotrimeric, consisting of a homodimer of accessory subunits plus a catalytic subunit. The protein encoded by this gene is the catalytic subunit of mitochondrial DNA polymerase. The encoded protein contains a polyglutamine tract near its N-terminus that may be polymorphic. Defects in this gene are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions 1 (PEOA1), sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO), Alpers-Huttenlocher syndrome (AHS), and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCI | NM_001113378.2 | c.*560A>G | 3_prime_UTR_variant | 38/38 | ENST00000310775.12 | ||
POLG | NM_002693.3 | c.3644-192T>C | intron_variant | ENST00000268124.11 | |||
POLGARF | NM_001406557.1 | c.*2916-192T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCI | ENST00000310775.12 | c.*560A>G | 3_prime_UTR_variant | 38/38 | 1 | NM_001113378.2 | P1 | ||
POLG | ENST00000268124.11 | c.3644-192T>C | intron_variant | 1 | NM_002693.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000210 AC: 32AN: 152196Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.000212 AC: 97AN: 457470Hom.: 0 Cov.: 4 AF XY: 0.000159 AC XY: 39AN XY: 244748
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GnomAD4 genome ? AF: 0.000210 AC: 32AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74360
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 20, 2015 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at