rs77136537

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_012188.5(FOXI1):c.575-59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00973 in 1,347,514 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0098 ( 18 hom., cov: 33)

Exomes 𝑓: 0.0097 ( 146 hom. )

Consequence

FOXI1
NM_012188.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.298

Publications

2 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 5-170107990-G-A is Benign according to our data. Variant chr5-170107990-G-A is described in ClinVar as [Benign]. Clinvar id is 1282730.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00976 (1487/152302) while in subpopulation SAS AF = 0.0297 (143/4818). AF 95% confidence interval is 0.0257. There are 18 homozygotes in GnomAd4. There are 890 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
FOXI1	NM_012188.5 link	c.575-59G>A	intron_variant	Intron 1 of 1	ENST00000306268.8	NP_036320.2
FOXI1	NM_144769.4 link	c.575-344G>A	intron_variant	Intron 1 of 1		NP_658982.1
FOXI1	XR_941092.2 link	n.781-59G>A	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXI1	ENST00000306268.8 link	c.575-59G>A		intron_variant	Intron 1 of 1	1	NM_012188.5	ENSP00000304286.5		Q12951-1
FOXI1	ENST00000449804.4 link	c.575-344G>A		intron_variant	Intron 1 of 1	1		ENSP00000415483.2		Q12951-2

Frequencies

GnomAD3 genomes

AF:

0.00978

AC:

1488

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.0119

Gnomad SAS

AF:

0.0299

Gnomad FIN

AF:

0.0444

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00816

Gnomad OTH

AF:

0.00526

GnomAD4 exome

AF:

0.00972

AC:

11621

AN:

1195212

Hom.:

146

AF XY:

0.0103

AC XY:

6239

AN XY:

607794

show subpopulations

African (AFR)

AF:

0.000672

AC:

AN:

28254

American (AMR)

AF:

0.0175

AC:

770

AN:

44002

Ashkenazi Jewish (ASJ)

AF:

0.00944

AC:

230

AN:

24352

East Asian (EAS)

AF:

0.0113

AC:

436

AN:

38440

South Asian (SAS)

AF:

0.0260

AC:

2088

AN:

80290

European-Finnish (FIN)

AF:

0.0471

AC:

2489

AN:

52798

Middle Eastern (MID)

AF:

0.00247

AC:

AN:

5270

European-Non Finnish (NFE)

AF:

0.00588

AC:

5120

AN:

870130

Other (OTH)

AF:

0.00882

AC:

456

AN:

51676

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

665

1330

1996

2661

3326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00976

AC:

1487

AN:

152302

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

890

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000818

AC:

AN:

41566

American (AMR)

AF:

0.0111

AC:

170

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00893

AC:

AN:

3472

East Asian (EAS)

AF:

0.0120

AC:

AN:

5182

South Asian (SAS)

AF:

0.0297

AC:

143

AN:

4818

European-Finnish (FIN)

AF:

0.0444

AC:

471

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00816

AC:

555

AN:

68028

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

159

239

318

398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00793

Hom.:

Bravo

AF:

0.00595

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 06, 2019

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

-0.90

CADD

Benign

0.84

(source)

DANN

Benign

0.48

PhyloP100

-0.30

Mutation Taster

=100/0

polymorphism

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over