rs55685928
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_012188.5(FOXI1):c.1014G>A(p.Ala338=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,601,568 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0079 ( 14 hom., cov: 33)
Exomes 𝑓: 0.0024 ( 13 hom. )
Consequence
FOXI1
NM_012188.5 synonymous
NM_012188.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.07
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 5-170108488-G-A is Benign according to our data. Variant chr5-170108488-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 768050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-170108488-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.07 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00787 (1198/152274) while in subpopulation AFR AF= 0.0222 (921/41550). AF 95% confidence interval is 0.021. There are 14 homozygotes in gnomad4. There are 585 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 14 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXI1 | NM_012188.5 | c.1014G>A | p.Ala338= | synonymous_variant | 2/2 | ENST00000306268.8 | |
FOXI1 | NM_144769.4 | c.729G>A | p.Ala243= | synonymous_variant | 2/2 | ||
FOXI1 | XR_941092.2 | n.1220G>A | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXI1 | ENST00000306268.8 | c.1014G>A | p.Ala338= | synonymous_variant | 2/2 | 1 | NM_012188.5 | P1 | |
FOXI1 | ENST00000449804.4 | c.729G>A | p.Ala243= | synonymous_variant | 2/2 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00787 AC: 1198AN: 152156Hom.: 14 Cov.: 33
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GnomAD3 exomes AF: 0.00384 AC: 930AN: 242238Hom.: 3 AF XY: 0.00357 AC XY: 466AN XY: 130598
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GnomAD4 exome AF: 0.00238 AC: 3456AN: 1449294Hom.: 13 Cov.: 34 AF XY: 0.00243 AC XY: 1745AN XY: 719064
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GnomAD4 genome ? AF: 0.00787 AC: 1198AN: 152274Hom.: 14 Cov.: 33 AF XY: 0.00786 AC XY: 585AN XY: 74442
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 07, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 04, 2019 | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
FOXI1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 13, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Autosomal recessive nonsyndromic hearing loss 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Computational scores
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Name
Calibrated prediction
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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