5-170108730-C-A

Position:

• chr5-170108730-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012188.5(FOXI1):​c.*119C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 791,022 control chromosomes in the GnomAD database, including 23,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7855 hom., cov: 32)
  • Exomes 𝑓: 0.20 (15707 hom.)
• Consequence: FOXI1 NM_012188.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.636

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-170108730-C-A is Benign according to our data. Variant chr5-170108730-C-A is described in ClinVar as [Benign]. Clinvar id is 352713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXI1	NM_012188.5	c.*119C>A		3_prime_UTR_variant	2/2	ENST00000306268.8	NP_036320.2
FOXI1	NM_144769.4	c.*119C>A		3_prime_UTR_variant	2/2		NP_658982.1
FOXI1	XR_941092.2	n.1462C>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXI1	ENST00000306268.8	c.*119C>A		3_prime_UTR_variant	2/2	1	NM_012188.5	ENSP00000304286.5
FOXI1	ENST00000449804.4	c.*119C>A		3_prime_UTR_variant	2/2	1		ENSP00000415483.2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42729 AN: 151986 Hom.: 7831 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.203 AC: 129781 AN: 638918 Hom.: 15707 Cov.: 8 AF XY: 0.201 AC XY: 69270 AN XY: 343906

Gnomad4 AFR exome AF: 0.518

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.459

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.281 AC: 42802 AN: 152104 Hom.: 7855 Cov.: 32 AF XY: 0.282 AC XY: 20966 AN XY: 74356

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.273

Alfa AF: 0.179 Hom.: 2932

Bravo AF: 0.294

Asia WGS AF: 0.341 AC: 1185 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.056
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs6873124; hg19: chr5-169535734;