Genetic Variant FOXI1:c.574+71T>C (chr5-170106602-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_012188.5(FOXI1):c.574+71T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,587,342 control chromosomes in the GnomAD database, including 85,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.27 ( 6281 hom., cov: 33)

Exomes 𝑓: 0.33 ( 79555 hom. )

Consequence

FOXI1
NM_012188.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0800

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 5-170106602-T-C is Benign according to our data. Variant chr5-170106602-T-C is described in ClinVar as [Benign]. Clinvar id is 1297806.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
FOXI1	NM_012188.5 link	c.574+71T>C	intron_variant	Intron 1 of 1	ENST00000306268.8	NP_036320.2
FOXI1	NM_144769.4 link	c.574+71T>C	intron_variant	Intron 1 of 1		NP_658982.1
FOXI1	XR_941092.2 link	n.635+71T>C	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXI1	ENST00000306268.8 link	c.574+71T>C		intron_variant	Intron 1 of 1	1	NM_012188.5	ENSP00000304286.5		Q12951-1
FOXI1	ENST00000449804.4 link	c.574+71T>C		intron_variant	Intron 1 of 1	1		ENSP00000415483.2		Q12951-2

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41503

AN:

152064

Hom.:

6287

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.260

GnomAD4 exome

AF:

0.331

AC:

474375

AN:

1435160

Hom.:

79555

AF XY:

0.331

AC XY:

235681

AN XY:

712230

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.347

Gnomad4 EAS exome

AF:

0.302

Gnomad4 SAS exome

AF:

0.335

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.343

Gnomad4 OTH exome

AF:

0.320

GnomAD4 genome

AF:

0.273

AC:

41487

AN:

152182

Hom.:

6281

Cov.:

AF XY:

0.272

AC XY:

20242

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.140

Gnomad4 AMR

AF:

0.314

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.295

Gnomad4 SAS

AF:

0.317

Gnomad4 FIN

AF:

0.239

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.257

Alfa

AF:

0.329

Hom.:

4720

Bravo

AF:

0.272

Asia WGS

AF:

0.283

AC:

980

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.76

CADD

Benign

8.6

DANN

Benign

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over