dbSNP rs7380481: FOXI1:c.575-508T>C (chr5-170107541-T-C) – 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.575-508T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,112 control chromosomes in the GnomAD database, including 6,414 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 0.28 ( 6414 hom., cov: 32)

Consequence

FOXI1
NM_012188.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.272

Publications

1 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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
FOXI1	NM_012188.5 link	c.575-508T>C	intron_variant	Intron 1 of 1	ENST00000306268.8	NP_036320.2
FOXI1	NM_144769.4 link	c.575-793T>C	intron_variant	Intron 1 of 1		NP_658982.1
FOXI1	XR_941092.2 link	n.780+480T>C	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXI1	ENST00000306268.8 link	c.575-508T>C		intron_variant	Intron 1 of 1	1	NM_012188.5	ENSP00000304286.5		Q12951-1
FOXI1	ENST00000449804.4 link	c.575-793T>C		intron_variant	Intron 1 of 1	1		ENSP00000415483.2		Q12951-2

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42087

AN:

151994

Hom.:

6420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.266

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

GnomAD4 genome

AF:

0.277

AC:

42072

AN:

152112

Hom.:

6414

Cov.:

AF XY:

0.276

AC XY:

20524

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.150

AC:

6222

AN:

41506

American (AMR)

AF:

0.317

AC:

4845

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1211

AN:

3466

East Asian (EAS)

AF:

0.295

AC:

1524

AN:

5164

South Asian (SAS)

AF:

0.317

AC:

1524

AN:

4804

European-Finnish (FIN)

AF:

0.238

AC:

2521

AN:

10596

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.343

AC:

23299

AN:

67976

Other (OTH)

AF:

0.263

AC:

554

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1563

3125

4688

6250

7813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.297

Hom.:

920

Bravo

AF:

0.276

Asia WGS

AF:

0.285

AC:

988

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

7.8

(source)

DANN

Benign

0.39

PhyloP100

0.27

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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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