Genetic Variant FOXI1:c.574+724A>G (chr5-170107255-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012188.5(FOXI1):c.574+724A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,146 control chromosomes in the GnomAD database, including 31,982 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.64 ( 31982 hom., cov: 33)

Consequence

FOXI1
NM_012188.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.957

Publications

6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
FOXI1	NM_012188.5 link	c.574+724A>G	intron_variant	Intron 1 of 1	ENST00000306268.8	NP_036320.2
FOXI1	NM_144769.4 link	c.574+724A>G	intron_variant	Intron 1 of 1		NP_658982.1
FOXI1	XR_941092.2 link	n.780+194A>G	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXI1	ENST00000306268.8 link	c.574+724A>G		intron_variant	Intron 1 of 1	1	NM_012188.5	ENSP00000304286.5		Q12951-1
FOXI1	ENST00000449804.4 link	c.574+724A>G		intron_variant	Intron 1 of 1	1		ENSP00000415483.2		Q12951-2

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

97391

AN:

152026

Hom.:

31957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.770

Gnomad AMI

AF:

0.674

Gnomad AMR

AF:

0.594

Gnomad ASJ

AF:

0.583

Gnomad EAS

AF:

0.822

Gnomad SAS

AF:

0.651

Gnomad FIN

AF:

0.549

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.576

Gnomad OTH

AF:

0.599

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.641

AC:

97459

AN:

152146

Hom.:

31982

Cov.:

AF XY:

0.641

AC XY:

47682

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.770

AC:

31960

AN:

41502

American (AMR)

AF:

0.594

AC:

9086

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.583

AC:

2023

AN:

3470

East Asian (EAS)

AF:

0.822

AC:

4243

AN:

5162

South Asian (SAS)

AF:

0.650

AC:

3131

AN:

4818

European-Finnish (FIN)

AF:

0.549

AC:

5819

AN:

10594

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.576

AC:

39172

AN:

67986

Other (OTH)

AF:

0.601

AC:

1271

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1761

3521

5282

7042

8803

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.562

Hom.:

3125

Bravo

AF:

0.647

Asia WGS

AF:

0.693

AC:

2408

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.18

(source)

DANN

Benign

0.59

PhyloP100

-0.96

Mutation Taster

=86/14

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over