rs72828668
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_012188.5(FOXI1):c.*331G>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 0.0221 in 294,548 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.020 ( 51 hom., cov: 33)
Exomes 𝑓: 0.024 ( 59 hom. )
Consequence
FOXI1
NM_012188.5 3_prime_UTR
NM_012188.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.390
Genes affected
FOXI1 (HGNC:3815): (forkhead box I1) This gene belongs to the forkhead family of transcription factors, which is characterized by a distinct forkhead domain. This gene may play an important role in the development of the cochlea and vestibulum, as well as in embryogenesis. The encoded protein has been found to be required for the transcription of four subunits of a proton pump found in the inner ear, the kidney, and the epididymis. Mutations in this gene have been associated with deafness, autosomal recessive 4. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 5-170108942-G-C is Benign according to our data. Variant chr5-170108942-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 904692.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXI1 | NM_012188.5 | c.*331G>C | 3_prime_UTR_variant | 2/2 | ENST00000306268.8 | ||
FOXI1 | NM_144769.4 | c.*331G>C | 3_prime_UTR_variant | 2/2 | |||
FOXI1 | XR_941092.2 | n.1674G>C | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXI1 | ENST00000306268.8 | c.*331G>C | 3_prime_UTR_variant | 2/2 | 1 | NM_012188.5 | P1 | ||
FOXI1 | ENST00000449804.4 | c.*331G>C | 3_prime_UTR_variant | 2/2 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0205 AC: 3115AN: 152136Hom.: 50 Cov.: 33
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GnomAD4 exome AF: 0.0238 AC: 3387AN: 142294Hom.: 59 Cov.: 0 AF XY: 0.0250 AC XY: 1838AN XY: 73630
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GnomAD4 genome ? AF: 0.0205 AC: 3115AN: 152254Hom.: 51 Cov.: 33 AF XY: 0.0224 AC XY: 1665AN XY: 74424
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at