rs2277944
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_012188.5(FOXI1):c.279G>A(p.Arg93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,577,604 control chromosomes in the GnomAD database, including 36,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.29 ( 8264 hom., cov: 32)
Exomes 𝑓: 0.18 ( 28604 hom. )
Consequence
FOXI1
NM_012188.5 synonymous
NM_012188.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.39
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 5-170106236-G-A is Benign according to our data. Variant chr5-170106236-G-A is described in ClinVar as [Benign]. Clinvar id is 352702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-170106236-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=2.39 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXI1 | NM_012188.5 | c.279G>A | p.Arg93= | synonymous_variant | 1/2 | ENST00000306268.8 | |
FOXI1 | NM_144769.4 | c.279G>A | p.Arg93= | synonymous_variant | 1/2 | ||
FOXI1 | XR_941092.2 | n.340G>A | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXI1 | ENST00000306268.8 | c.279G>A | p.Arg93= | synonymous_variant | 1/2 | 1 | NM_012188.5 | P1 | |
FOXI1 | ENST00000449804.4 | c.279G>A | p.Arg93= | synonymous_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.286 AC: 43513AN: 151974Hom.: 8239 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
43513
AN:
151974
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.231 AC: 43364AN: 187600Hom.: 6174 AF XY: 0.224 AC XY: 22614AN XY: 101130
GnomAD3 exomes
AF:
AC:
43364
AN:
187600
Hom.:
AF XY:
AC XY:
22614
AN XY:
101130
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.184 AC: 262761AN: 1425512Hom.: 28604 Cov.: 35 AF XY: 0.185 AC XY: 130440AN XY: 706096
GnomAD4 exome
AF:
AC:
262761
AN:
1425512
Hom.:
Cov.:
35
AF XY:
AC XY:
130440
AN XY:
706096
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.287 AC: 43587AN: 152092Hom.: 8264 Cov.: 32 AF XY: 0.287 AC XY: 21336AN XY: 74364
GnomAD4 genome
?
AF:
AC:
43587
AN:
152092
Hom.:
Cov.:
32
AF XY:
AC XY:
21336
AN XY:
74364
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1206
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Autosomal recessive nonsyndromic hearing loss 4 Benign:1
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 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:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at