rs10063424

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012188.5(FOXI1):c.1044T>C(p.Tyr348Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,609,276 control chromosomes in the GnomAD database, including 667,570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 62367 hom., cov: 32)

Exomes 𝑓: 0.91 ( 605203 hom. )

Consequence

FOXI1
NM_012188.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.667

Publications

29 publications found

Variant links:

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]

FOXI1 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 4
Inheritance: Unknown, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
autosomal recessive distal renal tubular acidosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Pendred syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss disorder
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
enlarged vestibular aqueduct syndrome
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

FOXI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 5-170108518-T-C is Benign according to our data. Variant chr5-170108518-T-C is described in ClinVar as [Benign]. Clinvar id is 260212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.667 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
FOXI1	NM_012188.5 link	c.1044T>C	p.Tyr348Tyr	synonymous_variant	Exon 2 of 2	ENST00000306268.8	NP_036320.2
FOXI1	NM_144769.4 link	c.759T>C	p.Tyr253Tyr	synonymous_variant	Exon 2 of 2		NP_658982.1
FOXI1	XR_941092.2 link	n.1250T>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXI1	ENST00000306268.8 link	c.1044T>C	p.Tyr348Tyr	synonymous_variant	Exon 2 of 2	1	NM_012188.5	ENSP00000304286.5		Q12951-1
FOXI1	ENST00000449804.4 link	c.759T>C	p.Tyr253Tyr	synonymous_variant	Exon 2 of 2	1		ENSP00000415483.2		Q12951-2

Frequencies

GnomAD3 genomes

AF:

0.905

AC:

137631

AN:

152150

Hom.:

62314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.897

Gnomad AMI

AF:

0.805

Gnomad AMR

AF:

0.912

Gnomad ASJ

AF:

0.940

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.931

Gnomad FIN

AF:

0.864

Gnomad MID

AF:

0.882

Gnomad NFE

AF:

0.905

Gnomad OTH

AF:

0.900

GnomAD2 exomes

AF:

0.911

AC:

225284

AN:

247330

AF XY:

0.911

show subpopulations

Gnomad AFR exome

AF:

0.898

Gnomad AMR exome

AF:

0.916

Gnomad ASJ exome

AF:

0.934

Gnomad EAS exome

AF:

0.987

Gnomad FIN exome

AF:

0.862

Gnomad NFE exome

AF:

0.901

Gnomad OTH exome

AF:

0.900

GnomAD4 exome

AF:

0.911

AC:

1327583

AN:

1457008

Hom.:

605203

Cov.:

AF XY:

0.912

AC XY:

660125

AN XY:

724206

show subpopulations

African (AFR)

AF:

0.898

AC:

30021

AN:

33422

American (AMR)

AF:

0.914

AC:

40658

AN:

44490

Ashkenazi Jewish (ASJ)

AF:

0.932

AC:

23996

AN:

25748

East Asian (EAS)

AF:

0.987

AC:

39130

AN:

39628

South Asian (SAS)

AF:

0.932

AC:

79713

AN:

85574

European-Finnish (FIN)

AF:

0.862

AC:

45849

AN:

53172

Middle Eastern (MID)

AF:

0.898

AC:

5154

AN:

5738

European-Non Finnish (NFE)

AF:

0.909

AC:

1008470

AN:

1109098

Other (OTH)

AF:

0.908

AC:

54592

AN:

60138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

6981

13963

20944

27926

34907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.905

AC:

137741

AN:

152268

Hom.:

62367

Cov.:

AF XY:

0.903

AC XY:

67236

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.897

AC:

37276

AN:

41556

American (AMR)

AF:

0.913

AC:

13954

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.940

AC:

3263

AN:

3472

East Asian (EAS)

AF:

0.986

AC:

5104

AN:

5174

South Asian (SAS)

AF:

0.931

AC:

4496

AN:

4830

European-Finnish (FIN)

AF:

0.864

AC:

9174

AN:

10614

Middle Eastern (MID)

AF:

0.884

AC:

258

AN:

292

European-Non Finnish (NFE)

AF:

0.905

AC:

61576

AN:

68012

Other (OTH)

AF:

0.902

AC:

1906

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

688

1376

2063

2751

3439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.905

Hom.:

122779

Bravo

AF:

0.907

Asia WGS

AF:

0.944

AC:

3281

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 4

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.020

(source)

DANN

Benign

0.18

PhyloP100

-0.67

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs10063424

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over